Search results for: healthy with induced pain

Authors: Boroka Gács, Tibor Szolcsányi, Árpad Csathó

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Background: Individuals frequently show habituation to repeated noxious heat. However, given the defensive function of human pain processing, it is reasonable to assume that individuals imagine that they would become increasingly sensitive to repeated thermal pain stimuli. To the best of the authors' knowledge, no previous studies have, however, been addressed to this assumption. Therefore, in the current study, we investigated how healthy human individuals imagine the intensity of repeated thermal pain stimulations, and compared this with the intensity ratings given after physically induced thermal pain trials. Methods: Healthy participants (N = 20) gave pain intensity ratings in two conditions: imagined and real thermal pain. In the real pain condition thermal pain stimuli of two intensities (minimal and moderate pain) were delivered in four consecutive trials. The duration of the peak temperature was 20s, and stimulation was always delivered to the same location. In each trial, participants rated the pain intensity twice, 5s and 15s after the onset of the peak temperature. In the imagined pain condition, participants were subjected to a reference pain stimulus and then asked to imagine and rate the same sequence of stimulations as in the induced pain condition. Results: Ratings of imagined pain and physically induced pain followed opposite courses over repeated stimulation: Ratings of imagined pain indicated sensitization whereas ratings for physically induced pain indicated habituation. The findings were similar for minimal and moderate pain intensities. Conclusions: The findings suggest that, rather than habituating to pain, healthy individuals imagine that they would become increasingly sensitive to repeated thermal pain stimuli.

Keywords: habituation, imagined pain, pain perception, thermal stimulation

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Authors: C. M. Segning, H. Ezzaidi, S. Nogomo, M. Otis

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Our proposal aims for developing an objective pain discrimination system, i.e., to discriminate between two neuronal conditions affecting the same neurophysiological signal. In this study, we present an approach to identify, in the first instance, two types of pain based on the analysis of the EEG signal decomposition coefficients. Each EEG segment of one-second duration is analyzed using the Chebyshev and linear prediction transform to extract a set of non-linear features, namely the Chebyshev and linear prediction coefficients. These features are used as the input vector of the Gaussian mixture model (GMM) for classification to differentiate two types of pain. To evaluate the performance of the proposed approach, we used an EEG dataset recorded in the left temporal (T7) and left frontocentral (FC5) regions. The experimental results demonstrate the effectiveness of Chebyshev coefficients for accurate differentiation of chronic fibromyalgia-like pain and experimental pain in the resting gamma band, with an accuracy of 93.9%. These results suggest a potential for discrimination of clinical pain according to its mechanism.

Keywords: chronic fibromyalgia pain, Chebyshev coefficients, healthy with induced pain, electroencephalogram, Gaussian mixture model

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Nantawan Soonklang, Linda Chularojanamontri, Urarat Nanna

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Ethnopharmacological relevance: Thunbergia laurifolia Lindl. belongs to the family Acanthaceae commonly known as Rang jeud in Thailand. This plant is traditionally used in Thailand for centuries as an antidote for several poisons and drug overdose. Aim of the study: This research aimed to study the analgesic and antipyretic activities of T. laurifolia water extract by using animal models. Materials and Methods: The analgesic activity was studied using 2 methods of pain induction including acetic acid and heat induced pain. And the antipyretic activity study was performed by yeast-induced hyperthermia. Results: The results showed that the administration of T. laurifolia extract possessed analgesic activity by reducing acetic acid-induced writhing response and heat-induced pain as well as showed antipyretic activity by decreasing body temperature of hyperthermic rats induced by brewer’s yeast. Conclusion: The study indicates that the T. laurifolia extract possesses analgesic and antipyretic activities in animals.

Keywords: Thunbergia laurifolia extract, analgesic activity, antipyretic activity, hyperthermia

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Authors: Linda Chularojmontri, Seewaboon Sireeratawong, Suvara Wattanapitayakul

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Terminalia arjuna Roxb. (family Combretaceae) is commonly known as ‘Sa maw thet’ in Thai. The fruit is used in traditional medicine as natural mild laxatives, carminative and expectorant. Aim of the study: This research aims to study the anti-inflammatory, analgesic and antipyretic activities of Terminalia arjuna extract by using animal models in comparison to the reference drugs. Materials and Methods: The anti-inflammatory study was conducted by two experimental animal models namely ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema. The study of analgesic activity used two methods of pain induction including acetic acid and heat-induced pain. In addition, the antipyretic activity study was performed by induced hyperthermia with yeast. Results: The results showed that the oral administration of Terminalia arjuna extract possessed acute anti-inflammatory effect in carrageenan-induced paw edema. Terminalia arjuna extract showed the analgesic activity in acetic acid-induced writhing response and heat-induced pain. This indicates its peripheral effect by inhibiting the biosynthesis and/or release of some pain mediators and some mechanism through Central nervous system. Moreover, Terminalia arjuna extract at the dose of 1000 and 1500 mg/kg body weight showed the antipyretic activity, which might be because of the inhibition of prostaglandins. Conclusion: The findings of this study indicated that the Terminalia arjuna extract possesses the anti-inflammatory, analgesic and antipyretic activities in animals.

Keywords: analgesic activity, anti-inflammatory activity, antipyretic activity, Terminalia arjuna extract

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Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

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There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

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Authors: Lídia E. O. Cruz, Adriano P. C. Calvo, Renato J. Soares, Regiane A. Carvalho

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Individuals with non-specific chronic low back pain may present altered movement patterns during functional activities. However, muscle behavior before and after performing a functional task with different load conditions is not yet fully understood. The aim of this study is to analyze lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground (with and without load) in individuals with nonspecific chronic low back pain. 20 subjects with nonspecific chronic low back pain and 20 healthy subjects participated in this study. A surface electromyography was performed in the ilio-costal, longissimus and multifidus muscles to evaluate lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground, with and without load. The symptomatic participants had greater lumbar muscle activation compared to the asymptomatic group, more evident in performing the task without load, with statistically significant difference (p = 0,033) between groups for the right multifidus muscle. This study showed that individuals with nonspecific chronic low back pain have higher muscle activation before and after performing a functional task compared to healthy participants.

Keywords: chronic low back pain, functional task, lumbar muscles, muscle activity

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Authors: Aman Upaganlawar, Chandrasekhar Upasani

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The present study was designed to screen the neuroprotective and antioxidant activity of corosolic acid in painful diabetic neuropathy (DN). Diabetes was induced in rats by single dose of STZ (60mg/kg, i.p). Diabetic rats were tested every week for the development of pain, at 5th week rats showed sensation of pain. At 6th week the rats developed significant neuropathic pain. They were divided into different groups and treated with Corosolic acid (2 and 4 mg/kg, p.o) for further two weeks. Pain was assessed in the diabetic rats by mechano-tactil allodynia, mechanical hyperalgesia and cold allodynia. At the end of treatment period rats were scarified and biochemical changes such as plasma glucose level, endogenous antioxidants (Lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) in sciatic nerve were evaluated. Further Na+/K+ ATPase and nitric oxide content was also evaluated. Treatment with corosolic acid for two weeks restored the altered body weight and elevated blood sugar level. Further corosolic acid showed dose dependent reduction in pain in neuropathic animals. The level of endogenous antioxidants enzymes, Na+/K+ ATPase and nitric oxide were significantly prevented. In conclusion, the result of the present study suggests the antidiabetic, antioxidant and neuroprotectieve property of corosolic acid in diabetic rats with neuropathic pain.

Keywords: neuropathic pain, diabetes, corosolic acid, antioxidant

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Authors: A. Estaji

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The first part of the present paper studies the role of language in expressing pain. Pain is usually described as a personal and mental experience, so language has an important role in describing, expressing and measuring pain and sometimes it is believed that language is the only device for accessing this personal experience. The second part of this paper studies gender differences in expressing pain. Considering the biological, psychological and social differences between men and women, we raise this question whether men and women express their pain in the same way or differently. To answer this question, we asked 44 Farsi speaking participants to write about the most painful experience they had in the past. Qualitative analysis of the data shows that women, have expressed their pain more severely, have expressed their feelings about pain instead of describing the pain itself, have made their pain more personal and have given more details about the circumstances in which they experienced pain, while men have given a more neutral description of their pain and have given a description of their pain by distancing themselves from the painful event. Knowing these gender differences in expressing pain can help medical practitioners in assessing the pain level.

Keywords: discourse analysis, expressing pain, measuring pain, gender

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Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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Authors: Aikaterini Amanatidou

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We describe the case of a 20-year-old female patient diagnosed with Ehlers-Danlos Syndrome (EDS) who was scheduled to undergo a wisdom teeth extraction in outpatient surgery. EDS is a hereditary connective tissue disorder characterized by joint hypermobility, skin hyper-extensibility, and vascular and soft tissue fragility. There are six subtypes of Ehlers-Danlos, and in our case, the patient had EDS hyper-mobility (HT) type disorder. One important clinical feature of this syndrome is chronic pain, which is often poorly understood and treated. Our patient had a long history of articular and lumbar pain when she was diagnosed. She was prescribed analgesic treatment for acute and neuropathic pain and had multiple sessions of psychotherapy and physiotherapy to ease the pain. Unfortunately, her extensive medical history was underrated by our anesthetic team, and no further measures were taken for the operation. Despite an uneventful intra-operative phase, the patient experienced several episodes of hyperalgesia during the immediate post-operative care. Management of pain was challenging for the anesthetic team: initial opioid treatment had only a temporary effect and a paradoxical reaction after a while. Final pain relief was eventually obtained with psycho-physiologic treatment, high doses of ketamine, and patient-controlled analgesia infusion of morphine-ketamine-dehydrobenzperidol. We suspected an episode of Opioid-Induced hyperalgesia. This case report supports the hypothesis that anti-hyperalgesics such as ketamine as well as lidocaine, and dexmedetomidine should be considered intra-operatively to avoid opioid-induced hyperalgesia and may be an alternative solution to manage complex chronic pain like others in neuropathic pain syndromes.

Keywords: Ehlers-Danlos, post-operative management, hyperalgesia, opioid-induced hyperalgesia, rare disease

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Authors: Watchawin Ekphinitphithaya, Patompong Satapornpong

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Introduction: Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs (AEDs) by neurologists and non-neurologist worldwide. CBZ is usually prescribed along with other drugs, leading to the possibility of severe cutaneous adverse drug reactions (SCARs). The HLA-B*15:02 is strongly associated with CBZ-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations, while HLA-A*31:01 allele has been reported to be associated with CBZ-induced SCARs in European population and Japanese. Objective: The aim of this study is to investigate the distribution of pharmacogenetics HLA-A*31:01 marker in a healthy Thai population associated with Carbamazepine-induced SCARs. Materials and Methods: Prospective study, 350 unrelated healthy Thais were recruited in this study. Human leukocyte antigen-A alleles were genotyped using PCR-sequence specific oligonucleotides (PCR-SSOs). Results: The frequency of HLA-A alleles were HLA-A*11:01 (190 alleles, 27.14%), HLA-A*24:02 (82 alleles, 11.71%), HLA-A*02:03 (80 alleles, 11.43%), HLA-A*33:03 (76 alleles, 10.86%), HLA-A*02:07 (58 alleles, 8.29%), HLA-A*02:01 (35 alleles, 5.00%), HLA-A*24:07 (29 alleles, 4.14%), HLA-A*02:06 – HLA-A*30:01 (15 alleles, 2.14%), and HLA-A*01:01 (14 alleles, 2.00%). Particularly, the number of HLA-A*31:01 alleles was 6 of 700 (0.86%) in the healthy Thai population. Many research presented varying distributions of HLA-A*31:01 in Asians, including 2% of Han Chinese, 9% of Japanese and 5% of Koreans. In addition, this allele was found approximately 2-5% in the Caucasian population. Conclusions: Thus, the pharmacogenetics database is vital to support in many populations, especially in Thais, for screening HLA-A*31:01 allele to avoid CBZ-induced SCARs before initiating treatments in each population.

Keywords: Carbamazepine, HLA-A*31:01, Thai population, pharmacogenetics

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Authors: Venus Pagare, Amit Kharat, Dhaval K. Thakkar, Tushar J. Palekar

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Introduction: Chronic low back pain (CLBP) is a major public health problem and is the leading musculoskeletal cause of disability. Altered neuromuscular control of core muscles, particulary transverses abdominis (TrA) is thought to be a contributing factor for the development of CLBP. Therefore, various exercises targeting the TrA are commonly incorporated into the rehabilitation. Objectives: To investigate the effects of 3 different core exercises on activation capacity of TrA muscle in individuals with CLBP as compared with healthy controls. Methodology: Thickness of TrA muscle was measured by ultrasound imaging in 30 patients with CLBP and 30 healthy controls. Measurements were taken during 3 different TrA activation exercises i.e Abdominal drawing in maneuver (ADIM), Abdominal drawing in with straight leg raise (ADSLR) and breathe hold at maximum expiration (ME). Thickness of the muscle at rest (at the end of normal tidal expiration) was taken as a baseline measure. Results: There was a significant difference between the healthy subjects and patients with low back pain with regard to the thickness of TrA at rest and thickness during contraction. ADIM produced a significant increase in the thickness of TrA compared to ADSLR and ME (p<0.001). Also, increase in thickness of TrA was more in the control group than patients with low back pain. Conclusion: CLBP patients exhibited atrophy of TrA muscle with delayed activation. Also, of the various core exercises, ADIM can be an effective method for activation of TrA.

Keywords: LBP, CLBP, ADSLR, ADIM

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Authors: Cinzia Cruder, Deborah Falla, Francesca Mangili, Laura Azzimonti, Liliana Araujo, Aaron Williamon, Marco Barbero

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Background and aims: According to the existing literature, musicians are at risk to experience a range of musculoskeletal painful conditions. Recently, digital technology has been developed to investigate pain location and pain extent. The aim of this study was to describe pain location and pain extent in musicians using a digital method for pain drawing analysis. Additionally, the association between pain drawing (PD) variables and clinical features in musicians with pain were explored. Materials and Methods: One hundred fifty-eight musicians (90 women and 68 men; age 22.4±3.6 years) were recruited from Swiss and UK conservatoires. Participants were asked to complete a survey including both background musical information and clinical features, the Quick Dash (QD) questionnaire and the digital PDs. Results: Of the 158 participants, 126 musicians (79.7%) reported having pain, with more prevalence in the areas of the neck and shoulders, the lower back and the right arm. The mean of pain extent was 3.1% ±6.5. The mean of QD was larger for musicians showing the presence of pain than for those without pain. Additionally, the results indicated a positive correlation between QD score and pain extent, and there were significant correlations between age and pain intensity, as well as between pain extent and pain intensity. Conclusions: The high prevalence of pain among musicians has been confirmed using a digital PD. In addition, positive correlations between pain extent and upper limb disability has been demonstrated. Our findings highlight the need for effective prevention and treatment strategies for musicians.

Keywords: pain location, pain extent, musicians, pain drawings

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Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Zarina Zahari, Maria Justine, Kamaria Kamaruddin

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Low back pain (LBP) is a major musculoskeletal problem in global population. This study aimed to examine the relationship between pain, disability and quality of life in patients with non-specific low back pain (LBP). One hundred LBP participants were recruited in this cross-sectional study (mean age = 42.23±11.34 years old). Pain was measured using Numerical Rating Scale (11-point). Disability was assessed using the revised Oswestry low back pain disability questionnaire (ODQ) and quality of life (QoL) was evaluated using the SF-36 v2. Majority of participants (58%) presented with moderate pain and 49% experienced severe disability. Thus, the pain and disability were found significant with negative correlation (r= -0.712, p<0.05). The pain and QoL also showed significant and positive correlation with both Physical Health Component Summary (PHCS) (r= .840, p<0.05) and Mental Health Component Summary (MHCS) (r= 0.446, p<0.05). Regression analysis indicated that pain emerged as an indicator of both disability and QoL (PHCS and MHCS) accounting for 51%, 71% and 21% of the variances respectively. This indicates that pain is an important factor in predicting disability and QoL in LBP sufferers.

Keywords: disability, low back pain, pain, quality of life

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Authors: Rachid El Khoury

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Chronic pain is perhaps the most burdensome health issue facing the planet. Our understanding of the pathophysiology of chronic pain has increased substantially over the past 25 years, including but not limited to changes in the brain. However, we still do not know why chronic pain develops in some people and not in others. Most of the recent developments in pain science, that have direct relevance to clinical management, relate to our understanding of the role of the brain, the role of the immune system, or the role of cognitive and behavioral factors. Although the Biopsychosocial model of pain management was presented decades ago, the Bio-reductionist model remains, unfortunately, at the heart of many practices across professional and geographic boundaries. A large body of evidence shows that nociception is neither sufficient nor necessary for pain. Pain is a conscious experience that can certainly be, and often is, associated with nociception, however, always modulated by countless neurobiological, environmental, and cognitive factors. This study will clarify the current misconceptions of chronic pain concepts, and their misperceptions by clinicians. It will also attempt to bridge the considerable gap between what we already know on pain but somehow disregarded, the development in pain science, and clinical practice.

Keywords: chronic pain, nociception, biopsychosocial, neuroplasticity

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Authors: Joe Collins, Matthias Rother

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Background: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of joint pain during and post-exercise. However, oral NSAIDs increase the risk of systemic side effects, even in healthy individuals, and retard recovery from muscle soreness. TDT 064 (Flexiseq®), a topical formulation containing ultra-deformable drug-free Sequessome™ vesicles, has demonstrated equivalent efficacy to oral celecoxib in reducing osteoarthritis-associated joint pain and stiffness. TDT 064 does not cause NSAID-related adverse effects. We describe clinical study data and a case report on the effectiveness of TDT 064 in reducing joint pain after exercise. Methods: Participants with a pain score ≥3 (10-point scale) 12–16 hours post-exercise were randomized to receive TDT 064 plus oral placebo, TDT 064 plus oral ketoprofen, or ketoprofen in ultra-deformable phospholipid vesicles plus oral placebo. Results: In the 168 study participants, pain scores were significantly higher with oral ketoprofen plus TDT 064 than with TDT 064 plus placebo in the 7 days post-exercise (P = 0.0240) and recovery from muscle soreness was significantly longer (P = 0.0262). There was a low incidence of adverse events. These data are supported by clinical experience. A 24-year-old male professional rugby player suffered a traumatic lisfranc fracture in March 2014 and underwent operative reconstruction. He had no relevant medical history and was not receiving concomitant medications. He had undergone anterior cruciate ligament reconstruction in 2008. The patient reported restricted training due to pain (score 7/10), stiffness (score 9/10) and poor function, as well as pain when changing direction and running on consecutive days. In July 2014 he started using TDT 064 twice daily at the recommended dose. In November 2014 he noted reduced pain on running (score 2-3/10), decreased morning stiffness (score 4/10) and improved joint mobility and was able to return to competitive rugby without restrictions. No side effects of TDT 064 were reported. Conclusions: TDT 064 shows efficacy against exercise- and injury-induced joint pain, as well as that associated with osteoarthritis. It does not retard muscle soreness recovery after exercise compared with an oral NSAID, making it an alternative approach for the treatment of joint pain during and post-exercise.

Keywords: exercise, joint pain, TDT 064, phospholipid vesicles

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Authors: Nanditha Rajamani, Anirudhaa R. Rao, Divya Sriram

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One of the greatest difficulties in treating patients with pain is the highly subjective nature of pain sensation. The measurement of pain intensity is primarily dependent on the patient’s report, often with little physical evidence to provide objective corroboration. This is also complicated by the fact that there are only few and expensive existing technologies (Functional Magnetic Resonance Imaging-fMRI). The need is thus clear and urgent for a reliable, non-invasive, non-painful, objective, readily adoptable, and coefficient diagnostic platform that provides additional diagnostic information to supplement its current regime with more information to assist doctors in diagnosing these patients. Thus, our idea of developing a pain detector was conceived to take a step further the detection and diagnosis of chronic and acute pain.

Keywords: pain sensor, microwave radiometery, pain sensation, fMRI

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Authors: Kun Hua O., Dong Woon Kim, Won Hyung Lee

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Introduction: Neuropathic pain induced by spinal or peripheral nerve injury is highly resistant to common painkillers, nerve blocks, and other pain management approaches. Recently, several new therapeutic drug candidates have been developed to control neuropathic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate the ability of intrathecal or intravenous Evans blue to decrease pain behavior and to study the relationship between Evans blue and the neural structure of pain transmission. Method: Neuropathic pain (allodynia) of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats(n=10) in each group. Evans blue (5, 15, 50μg/10μl) or phosphate buffer saline(PBS,10μl) was injected intrathecally at 3days post-ligation or intravenously(1mg/200 μl) 3days and 5days post-ligation . Mechanical sensitivity was assessed using Von Frey filaments at 3 days post-ligation and at 2 hours, days 1, 2, 3, 5,7 after intrathecal Evans blue injection, and on days 2, 4, 7, and 11 at 14 days after intravenous injection. In the intrathecal group, microglia and glutaminergic neurons in the dorsal horn and VNUT(vesicular nucleotide transporter) in the dorsal root ganglia were tested to evaluate co-staining with Evans blue. The experimental procedures were performed in accordance with the animal care guideline of the Korean Academy of Medical Science(Animal ethic committee of Chungnam National University Hospital: CNUH-014-A0005-1). Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw 3 days post-ligation. Intrathecal Evans blue most significantly(P＜0.001) alleviated allodynia at 2 days after intrathecal, but not an intravenous injection. Glutaminergic neurons in the dorsal horn and VNUT in the dorsal root ganglia were co-stained with Evans blue. On the other hand, microglia in the dorsal horn were partially co-stained with Evans blue. Conclusion: We confirmed that Evans blue might have an analgesic effect through the central nervous system, not another system in neuropathic pain of the SNL animal model. These results suggest Evans blue may be a potential new drug for the treatment of chronic pain. This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C100757512), funded by the Ministry of Education.

Keywords: neuropathic pain, Evas blue, intrathecal, intravenous

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Authors: D. Schafer, H. Booke, R. Nordmeier

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Patients suffering from chronic musculoskeletal pain ( > 12 months) are a challenging clientele for pain specialists. A multimodal approach, characterized by a two weeks inpatient treatment, often is the ultimate therapeutic attempt. The lasting effects of such a multimodal approach were analyzed, especially since two weeks of inpatient therapy, although very intense, often seem too short to make a difference in patients suffering from chronic pain for years. The study includes 32 consecutive patients suffering from chronic pain over years who underwent a two weeks multimodal inpatient treatment of pain. Twelve months after discharge, each patient was interviewed to objectify any lasting effects. Pain was measured on admission and 12 months after discharge using the numeric rating scale (NRS). For statistics, a paired students' t-test was used. Significance was defined as p < 0.05. The average intensity of pain on admission was 8,6 on the NRS. Twelve months after discharge, the intensity of pain was still reduced by an average of 48% (average NRS 4,4), p < 0.05. Despite this significant improvement in pain severity, two thirds (66%) of the patients still judge their treatment as not sufficient. In conclusion, inpatient treatment of chronic pain has a long-lasting effect on the intensity of pain in patients suffering from chronic musculoskeletal pain for more than 12 months.

Keywords: chronic pain, inpatient treatment, multimodal pain treatment, musculoskeletal pain

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Authors: Nisrine Chlif, Mohammed Diouri, Amar Bentayeb

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Background: The Leaves of Brocchia cinerea (Vis.) (Asteraceae) is used traditionally and ethnomedicinally to alleviate pain, fever, and inflammation conditions. Objective: The current study investigates the anti-inflammatory, analgesic, and antipyretic activities of aqueous extract of the leaves of Brocchia cinerea (LBC). Material and methods: The extract was screened for anti-inflammatory (carrageenan-induced paw edema) and analgesic (acetic acid-induced writhing) activities in Wistar rats. Before acetic acid or carrageenan injection, rats were orally fed LBC (200 and 400 mg/ kg), Indomethacin (10 mg/kg), or Aspirin (100 mg/kg). The antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug. Results: The crude extract tested significantly prevented the increase in paw volume as compared to the control at 200 mg/kg and 400 mg/kg. The LBC treatment significantly inhibited pain at 400 mg/kg with a percent inhibition of 55.82%, as well as showing a significant reduction in hyperpyrexia in rats at 400 mg/kg. LBC extract produced a comparable activity to paracetamol at 100 mg/kg (p <0.01). Conclusion: The results of the present study that the leaves of B. cinerea extract exhibited strongly anti-inflammatory, analgesic, and antipyretic properties and justify the traditional use of this plant in inflammation, pain, and fever.

Keywords: analgesic, anti-inflammation, antipyretic, brocchia cinerea

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Authors: Valeriu Mihai But, Sorana Daniela Bolboacă, Adriana Elena Bulboacă

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The nutraceutical compound Curcumin (Curcuma longa L.) is known for its anti-inflammatory, anti-cancer, and antioxidant effects. This study aimed to evaluate the antioxidative and analgesic effects of Curcumin (CC) compared to Tramadol (T) in chemical-induced nociceptive pain in rats. Thirty-five rats were randomly divided into five groups of seven rats each and were treated as follows: C group (control group): treated with saline solution 0.9%, (1 ml, i.p. administration), ethanoic acid (EA) group: pretreated with saline solution 0.9% - 30 min before EA nociceptive pain induction, (1 ml, i.p. administration), T group: pretreated with Tramadol, 10 mg/kg body weight (bw), i.p. administration - 30 min before EA nociceptive pain induction, CC1-group: pretreated with 1 mg/100g bw Curcumin i.p. administration - 2 days before EA pain induction and CC2-group: pretreated with Curcumin 2 mg/100g bw i.p. administration - 2 days before EA nociceptive pain induction. The following oxidative stress parameters were assessed: malondialdehyde (MDA), nitric oxide (NOx), total oxidative status (TOS), total antioxidative capacity (TAC), and thiol (Th). The antalgic activity was measured by the ethanoic acid writhing test. Treatment with Curcumin, both 1 mg/100g bw, and 2 mg/100g bw, showed significant differences as compared with the control group (p<0.001) regarding malondialdehyde (MDA), nitric oxide (NOx), and total oxidative status (TOS) oxidative biomarkers. Pretreatment with 2 mg/100g bw of Curcumin presented a significant decrease in MDA values compared with Tramadol (p<0.001). The TAC significantly increased in pretreatment with Curcumin compared with group control. (p<0.001) The nociceptive response to EA was significantly reduced in Curcumin and Tramadol groups. Treatment with Curcumin at a higher concentration was more effective. In an experimental pain model, this study demonstrates an important antioxidant and antinociceptive activity of Curcumin comparable with Tramadol treatment.

Keywords: curcumin, nociception, oxidative stress, pain

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Authors: Minna Chang

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Introduction: M. pneumoniae is a respiratory pathogen, which commonly causes upper and lower respiratory infections. It primarily affects children and young adults. Respiratory symptoms are well recognized, but extrapulmonary involvement is also common. Other systems that have been implicated in the disease include: skin, mucus membranes, central, peripheral nervous systems, cardiovascular, haematological, renal, and musculoskeletal systems. Here, we report a case of an otherwise healthy, young female with M. pneumonia, who presented with right upper quadrant abdominal pain. Case presentation: a healthy 25-year-old female was referred to A&E by her general practitioner, after presenting with fever, malaise, and right upper quadrant pain. M. pneumoniae was confirmed retrospectively by serology. The patient made a full recovery after a six-day course of doxycycline 100mg. Conclusion: M. pneumonia is a well-established cause of respiratory infections in children and young adults. Febrile illness with multisystem involvement, even in the absence of respiratory symptoms, should raise suspicion of M. pneumoniae infection in healthy, young adults. Our case illustrates the multi-system involvement of M. pneumoniae, which was initially missed, due to paucity of respiratory symptoms at presentation.

Keywords: infectious diseases, mycoplasma pneumoniae, respiratory infections, extra-pulmonary manifestations

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Authors: Yi-Fung Lin, Yuan-Mei Liao

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Background: Pain is common among patients with cancer and is also one of the most disturbing symptoms. As this suffering is subjective, if patients proactively participate in their pain self-management, pain could be alleviated effectively. However, not everyone can carry out self-management very well because human behavior is a product of the cognition process. In this process, we can see that "self-efficacy" plays an essential role in affecting human behaviors. Methods: We used the eight steps of concept analysis proposed by Walker and Avant to clarify the concept of “self-efficacy for cancer pain management.” A comprehensive literature review was conducted for relevant publications that were published during the period of 1977 to 2021. We used several keywords, including self-efficacy, self-management, concept analysis, conceptual framework, and cancer pain, to search the following databases: PubMed, CINAHL, Web of Science, and Embase. Results: We identified three defining attributes for the concept of self-efficacy for cancer pain management, including pain management abilities, confidence, and continuous pain monitoring, and recognized six skills related to pain management abilities: problem-solving, decision-making, resource utilization, forming partnerships between medical professionals and patients, planning actions, and self-regulation. Five antecedents for the concept of self-efficacy for cancer pain management were identified: pain experience, existing cancer pain, pain-related knowledge, a belief in pain management, and physical/mental state. Consequences related to self-efficacy for cancer pain management were achievement of pain self-management, well pain control, satisfying quality of life, and containing motivation. Conclusions: This analysis provides researchers with a clearer understanding of the concept of “self-efficacy for cancer pain management.” The findings presented here provide a foundation for future research and nursing interventions to enhance self-efficacy for cancer pain management.

Keywords: cancer pain, concept analysis, self-efficacy, self-management

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Authors: Anna Mucha, Ewa Wojtyna, Anita Pollak

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The environment in which an individual resides and observes may play a meaningful role in well-being and related constructs. Contact with nature may have a positive influence of natural environments on individuals, impacting mood and psychophysical sensations, such as pain relief. Conversely, urban settings, dominated by concrete elements, might lead to mood decline and heightened stress levels. Similarly, the situation may appear in the case of the perception of virtual environments. However, this is a topic that requires further exploration, especially in the context of relationships with pain. The aforementioned matters served as the basis for formulating and executing the outlined experimental research within the realm of environmental psychology, leveraging new technologies, notably virtual reality (VR), which is progressively gaining prominence in the domain of mental health. The primary objective was to investigate the impact of a simulated virtual environment, mirroring a natural setting abundant in greenery, on the perception of acute pain induced by thermal stimuli (high temperature) – encompassing intensity, unpleasantness, and pain tolerance. Comparative analyses were conducted between the virtual natural environment (intentionally constructed in the likeness of a therapeutic garden), virtual urban environment, and a control group devoid of virtual projections. Secondary objectives aimed to determine the mutual relationships among variables such as positive and negative emotions, preferences regarding virtual environments, sense of presence, and restorative experience in the context of the perception of presented virtual environments and induced thermal pain. The study encompassed 126 physically healthy Polish adults, distributing 42 individuals across each of the three comparative groups. Oculus Rift VR technology and the TSA-II neurosensory analyzer facilitated the experiment. Alongside demographic data, participants' subjective feelings concerning virtual reality and pain were evaluated using the Visual Analogue Scale (VAS), the original Restorative Experience in the Virtual World questionnaire (Doświadczenie Regeneracji w Wirtualnym Świecie), and an adapted Slater-Usoh-Steed (SUS) questionnaire. Results of statistical and psychometric analyses, such as Kruskal-Wallis tests, Wilcoxon tests, and contrast analyses, underscored the positive impact of the virtual natural environment on individual pain perception and mood. The virtual natural environment outperformed the virtual urban environment and the control group without virtual projection, particularly in subjective pain components like intensity and unpleasantness. Variables such as restorative experience, sense of presence and virtual environment preference also proved pivotal in pain perception and pain tolerance threshold alterations, contingent on specific conditions. This implies considerable application potential for virtual natural environments across diverse realms of psychology and related fields, among others as a supportive analgesic approach and a form of relaxation following psychotherapeutic sessions.

Keywords: environmental psychology, nature, acute pain, emotions, vitrual reality, virtual environments

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Authors: Farah Al Zaabi, Sarah Amrani

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Complex regional pain syndrome (CRPS) is a chronic pain condition that develops in an extremity following a fracture, soft tissue injury, or surgery. It is a neuropathic pain disorder that is accompanied by the characteristic skin manifestations that are needed for the diagnosis. We report the case of a 30 year old male, who has findings consistent with CRPS and has been followed for over two years by multiple specialties within the healthcare system without obtaining a diagnosis. The symptoms he presented with were treated based on the specialty he was seeing, rather than unified and recognized as a single disease process. Our case highlights the complexity of chronic pain, which can sometimes present with skin manifestations, and the importance of involving a pain specialist early for both the medical and physical recovery of CRPS patients.

Keywords: complex regional pain syndrome, chronic pain, skin changes of CRPS, dermatological manifestions of CRPS

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Authors: Chalermsri Sorasit, Siriporn Mongkhonthawornchai, Darawan Augsornwan, Sudthanom Kamollirt

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Background: Although knowledge of pain and pain management is improving, they are still inadequate to patients. The Nursing Division of Srinagarind Hospital is responsible for setting the pain management system, including work instruction development and pain management indicators. We have developed an information technology program for monitoring pain quality indicators, which was implemented to all nursing departments in April 2013. Objective: To study outcomes of acute pain management in process and outcome indicators. Method: This is a retrospective descriptive study. The sample population was patients who had acute pain 24-48 hours after receiving a procedure, while admitted to Srinagarind Hospital in 2014. Data were collected from the information technology program. 2709 patients with acute pain from 10 Nursing Departments were recruited in the study. The research tools in this study were 1) the demographic questionnaire 2) the pain management questionnaire for process indicators, and 3) the pain management questionnaire for outcome indicators. Data were analyzed and presented by percentages and means. Results: The process indicators show that nurses used pain assessment tool and recorded 99.19%. The pain reassessment after the intervention was 96.09%. The 80.15% of the patients received opioid for pain medication and the most frequency of non-pharmacological intervention used was positioning (76.72%). For the outcome indicators, nearly half of them (49.90%) had moderate–severe pain, mean scores of worst pain was 6.48 and overall pain was 4.08. Patient satisfaction level with pain management was good (49.17%) and very good (46.62%). Conclusion: Nurses used pain assessment tools and pain documents which met the goal of the pain management process. Patient satisfaction with pain management was at high level. However the patients had still moderate to severe pain. Nurses should adhere more strictly to the guidelines of pain management, by using acute pain guidelines especially when pain intensity is particularly moderate-high. Nurses should also develop and practice a non-pharmacological pain management program to continually improve the quality of pain management. The information technology program should have more details about non-pharmacological pain techniques.

Keywords: outcome, pain management, acute pain, Srinagarind Hospital

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Authors: Shao-Cyuan Yewang, Yu-Wen Chen

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Background: Exercise training is well known to alleviate chronic pain syndromes improve of chronic pain. This study investigated the effect of swimming exercise training on thoracotomy and rib retraction-induced allodynia. Methods: Male Sprague Dawley rats that received animal model of persistent postthoracotomy pain. All rats were divided into three groups: sham operations group (Sham), thoracotomy and rib retraction group (TRR), and TRR with swimming exercise training for 90min/day, 7 days a week for 4 weeks (TRR-SEW). The sham group did not receive retraction of the ribs. Thus, they received a pleural incision. The levels of mechanical and cold allodynia were measured by von Frey and acetone test. Results: In von Frey test, the level of mechanical allodynia in the TRR group was significantly higher than the sham group. The level of mechanical allodynia in the TRR-SEW group was significantly lower than the TRR group. In acetone test, the level of cold allodynia in the TRR group was significantly higher than the sham group. The level of cold allodynia in the TRR-SEW group was significantly lower than the TRR group. Conclusions: These results suggest that swimming exercise training decreases persistent postthoracotomy pain caused by TRR surgery. It may provide one of the new therapeutic effects of swimming exercise training could alleviate persistent postthoracotomy pain.

Keywords: chronic pain, thoracotomy pain, swimming, von Frey test, acetone test

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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