Displaying publications 41 - 60 of 97 in total

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  1. Satyam SM, Bairy LK, Shetty P
    Neuroendocrinology, 2023;113(6):667-677.
    PMID: 36796342 DOI: 10.1159/000529761
    INTRODUCTION: Differences in pain thresholds may have implications in pain management, as they may account in part for the variability in analgesic requirements between individuals. We planned to investigate the influence of endogenous sex hormones on the analgesic modulation of tramadol in lean and high-fat diet-induced obese Wistar rats.

    METHODS: The whole study was carried out on 48 adult Wistar rats (24 male: 12 obese and 12 lean and 24 female: 12 obese and 12 lean). Each male and female rat group was further subdivided into two groups (n = 6/group) and treated with normal saline/tramadol for 5 days. On the fifth day, 15 min after tramadol/normal saline treatment, animals were tested for pain perception toward noxious stimuli. Later, endogenous 17 beta-estradiol and free testosterone levels in serum were estimated through ELISA methods.

    RESULTS: The present study revealed that female rats experienced more pain sensitivity to noxious stimuli compared to male rats. High-fat diet-induced obese rats experienced more pain sensations to noxious stimuli than lean rats. Obese male rats were found to have significantly low free testosterone and high 17 beta-estradiol levels compared to lean male rats. An increase in serum 17 beta-estradiol level led to increased pain sensation to noxious stimuli. While an increase in free testosterone level resulted in the lowering of pain sensation to noxious stimuli.

    CONCLUSION: The analgesic effect of tramadol was more pronounced in male rats compared to female rats. The analgesic effect of tramadol was more marked in lean rats compared to obese rats. Additional research to elucidate obesity-induced endocrine changes and the mechanisms driving sex hormones in pain perception is needed to foster future interventions to reduce disparities in pain.

    Matched MeSH terms: Pain/drug therapy
  2. Sakeena MH, Yam MF, Elrashid SM, Munavvar AS, Azmin MN
    J Oleo Sci, 2010;59(12):667-71.
    PMID: 21099145
    Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.
    Matched MeSH terms: Pain/drug therapy
  3. Saad LB, Hwi KK, Quah T
    PMID: 25371587
    BACKGROUND: There are severe adverse effects of analgesic drugs on human body. Extraction of analgesic drugs from natural products has therefore become the prime objective of the study. In this study, we aimed to evaluate the antinociceptive activity of the pomegranate fruit.

    MATERIALS AND METHODS: Antinociceptive activity of ethanol pomegranate extract was examined using three models of pain: the writhing test, the hot tail flick test and the plantar test. The ethanolic extract of pomegranate was administered by oral gavages in doses of (100,150 and 200mg/kg, p.o (orally)), for all the tests and compared with aspirin (100mg/kg, p.o.) which was considered as the standard drug. Phytochemical screening and HPLC analysis of the plant species was carried out.

    RESULTS: In the writhing test, the index of pain inhibition (IPI) was 37% for ethanolic extract of pomegranate (200mg/kg, p.o.), and 59% for aspirin. In the hot tail flick test, the ethanolic extract of pomegranate (200mg/kg, p.o.), has shown significant analgesia reaching its peak at 60 min maximum possible analgesia (MPA), was 24.1% as compared with aspirin 37.5%. Hyperalgesia was successfully induced by the plantar test and the ethanol extract of pomegranate (100,150,200mg/kg, p.o.), reduced the hyperalgesia in a dose dependent manner comparable to aspirin at (100mg/kg, p.o.). HPLC analysis revealed the presence of gallic acid, ellagic acid and Punicalagins A&B.

    CONCLUSION: The results demonstrated that ethanol pomegranate extract has an antinociceptive effect that may be related to the presence of identified phytochemicals.

    Matched MeSH terms: Pain/drug therapy*
  4. Rahman NH, DeSilva T
    J Emerg Med, 2012 Dec;43(6):951-7.
    PMID: 23068783 DOI: 10.1016/j.jemermed.2012.02.069
    The use of patient-controlled analgesia (PCA) has been reported to provide effective pain relief, often resulting in less opioid consumption, and is associated with greater patient satisfaction when it is compared to other techniques of analgesia delivery.
    Matched MeSH terms: Acute Pain/drug therapy*
  5. Rahman NH, DeSilva T
    Eur J Emerg Med, 2012 Aug;19(4):241-5.
    PMID: 21968714 DOI: 10.1097/MEJ.0b013e32834bfc17
    Pain seems to be one of the most frequent complaints in the emergency department, however pain control is often suboptimal as seen by many audits. We conducted a study to find out whether the use of patient control analgesia (PCA) is effective in controlling acute pain in the emergency department
    Matched MeSH terms: Pain/drug therapy*
  6. Puttarak P, Sawangjit R, Chaiyakunapruk N
    J Ethnopharmacol, 2016 Dec 24;194:316-323.
    PMID: 27620659 DOI: 10.1016/j.jep.2016.09.021
    ETHNOPHARMACOLOGICAL RELEVANCE: Derris scandens (Roxb.) Benth. has been used as active ingredient in Thai traditional medicine recipes for pain treatment. Dry stem powder and ethanolic extract also recommended in Thailand National List of Essential Medicines (NLEMs) for musculoskeletal pain treatment as herbal medicine. However, no summarization of clinical effect and safety has been evaluated.

    OBJECTIVE: Our study aimed to determine the clinical effects and safety of D. scandens for musculoskeletal pain treatment compared with standard regimen, nonsteroidal anti-inflammatory drugs (NSAIDs).

    METHODS: International and Thai databases were searched from inception through August 2015. Comparative randomized controlled trials investigating oral D. scandens for musculoskeletal pain were included. Outcomes of interest included level of pain and adverse event. Mean changes of the outcomes from baseline were compared between D. scandens and NSAIDs by calculating mean difference.

    RESULTS: From 42 articles identified, 4 studies involving a total of 414 patients were included for efficacy analysis. The effects of oral D. scandens on reducing pain score were no different from those of non-steroidal anti-inflammatory drugs at any time points (3, 7, 14 days and overall). The overall pain reduction in the D. scandens group was not inferior to treatment with NSAIDs (weighted mean difference 0.06; 95% CI: -0.20, 0.31) without evident of heterogeneity (I(2)=0.00%, p=0.768). When compared, the adverse events (AEs) of D. scandens showed no different relative risk with NSAIDs. The major adverse events were gastrointestinal symptoms.

    CONCLUSION: D. scandens may be considered as an alternative for musculoskeletal pain reduction.

    Matched MeSH terms: Musculoskeletal Pain/drug therapy*
  7. Ping CP, Tengku Mohamad TAS, Akhtar MN, Perimal EK, Akira A, Israf Ali DA, et al.
    Molecules, 2018 Sep 03;23(9).
    PMID: 30177603 DOI: 10.3390/molecules23092237
    Pain is one of the most common cause for hospital visits. It plays an important role in inflammation and serves as a warning sign to avoid further injury. Analgesics are used to manage pain and provide comfort to patients. However, prolonged usage of pain treatments like opioids and NSAIDs are accompanied with undesirable side effects. Therefore, research to identify novel compounds that produce analgesia with lesser side effects are necessary. The present study investigated the antinociceptive potentials of a natural compound, cardamonin, isolated from Boesenbergia rotunda (L) Mansf. using chemical and thermal models of nociception. Our findings showed that intraperitoneal and oral administration of cardamonin (0.3, 1, 3, and 10 mg/kg) produced significant and dose-dependent inhibition of pain in abdominal writhing responses induced by acetic acid. The present study also demonstrated that cardamonin produced significant analgesia in formalin-, capsaicin-, and glutamate-induced paw licking tests. In the thermal-induced nociception model, cardamonin exhibited significant increase in response latency time of animals subjected to hot-plate thermal stimuli. The rota-rod assessment confirmed that the antinociceptive activities elicited by cardamonin was not related to muscle relaxant or sedative effects of the compound. In conclusion, the present findings showed that cardamonin exerted significant peripheral and central antinociception through chemical- and thermal-induced nociception in mice through the involvement of TRPV₁, glutamate, and opioid receptors.
    Matched MeSH terms: Pain/drug therapy*
  8. Pan KL, Ibrahim S
    Med J Malaysia, 2000 Sep;55 Suppl C:107-8.
    PMID: 11200037
    Osteopoikilosis is a rare, inheritable, sclerosing bone dysplasia; sometimes mistaken for osteoblastic bone metastases. We report a case in a 25 year-old lady.
    Matched MeSH terms: Back Pain/drug therapy
  9. Pabreja K, Dua K, Sharma S, Padi SS, Kulkarni SK
    Eur J Pharmacol, 2011 Jul 1;661(1-3):15-21.
    PMID: 21536024 DOI: 10.1016/j.ejphar.2011.04.014
    Painful neuropathy, a common complication of diabetes mellitus is characterized by allodynia and hyperalgesia. Recent studies emphasized on the role of non-neuronal cells, particularly microglia in the development of neuronal hypersensitivity. The purpose of the present study is to evaluate the effect of minocyline, a selective inhibitor of microglial activation to define the role of neuroimmune activation in experimental diabetic neuropathy. Cold allodynia and thermal and chemical hyperalgesia were assessed and the markers of inflammation and oxidative and nitrosative stress were estimated in streptozotocin-induced diabetic rats. Chronic administration of minocycline (40 and 80 mg/kg, i.p.) for 2 weeks started 2 weeks after diabetes induction attenuated the development of diabetic neuropathy as compared to diabetic control animals. In addition, minocyline treatment reduced the levels of interleukin-1β and tumor necrosis factor-α, lipid peroxidation, nitrite and also improved antioxidant defense in spinal cords of diabetic rats as compared to diabetic control animals. In contrast, minocycline (80 mg/kg, per se) had no effect on any of these behavioral and biochemical parameters assessed in age-matched control animals. The results of the present study strongly suggest that activated microglia are involved in the development of experimental diabetic neuropathy and minocycline exerted its effect probably by inhibition of neuroimmune activation of microglia. In addition, the beneficial effects of minocycline are partly mediated by its anti-inflammatory effect by reducing the levels of proinflammatory cytokines and in part by modulating oxidative and nitrosative stress in the spinal cord that might be involved in attenuating the development of behavioral hypersensitivity in diabetic rats.
    Matched MeSH terms: Pain/drug therapy*
  10. Ong T, Thiam CN
    Clin Med (Lond), 2022 Jul;22(4):295-297.
    PMID: 35882494 DOI: 10.7861/clinmed.CM-2022-0273
    Pain is common among older people. However, it remains underrecognised and under-treated. A comprehensive assessment of pain involves identifying its cause, establishing its severity, determining its impact on the person experiencing it and reviewing the person's response to treatment. Addressing their pain requires a different approach compared to a younger person because there is usually concomitant frailty, multimorbidity, polypharmacy, sensory deficits and cognitive impairment. This review will summarise a comprehensive approach to pain management in the older person.
    Matched MeSH terms: Pain/drug therapy
  11. Ong HM, Mohamad AS, Makhtar N', Khalid MH, Khalid S, Perimal EK, et al.
    J Ethnopharmacol, 2011 Jan 7;133(1):227-33.
    PMID: 20920570 DOI: 10.1016/j.jep.2010.09.030
    Acmella uliginosa (Sw.) Cass. is a medicinal herbaceous plant that is commonly used by the Malay community in Malaysia to relieve pain often associated with mouth ulcers, toothache, sore throat, and stomach ache.
    Matched MeSH terms: Pain/drug therapy*
  12. Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.
    Sci Rep, 2021 12 16;11(1):24121.
    PMID: 34916536 DOI: 10.1038/s41598-021-02961-1
    A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.
    Matched MeSH terms: Pain/drug therapy*
  13. Ngeow WC, Nair R
    PMID: 20219585 DOI: 10.1016/j.tripleo.2009.03.021
    This article illustrates a case of persistent trigeminal neuralgia in a medically compromised 65-year-old female who did not respond to pharmacotherapy. She had undergone several peripheral neurectomies as well as a failed right posterior fossa exploration that resulted in a cerebrospinal fluid leak. Persistent pain over the right external nasal area and right mental region was relieved for several hours after daily injections of bupivacaine. A trial of a single dose of 100 units of botulinum toxin type A (BOTOX) diluted in 2.5 mL saline was injected into the external nasal trigger zone (60 units) and to the mental nerve region (40 units). She achieved complete pain relief in the external nasal region for 5 months. Pain recurred and the site was again injected with 100 units of botulinum toxin type A (BOTOX). Pain relief at the mental region was partial. This was finally controlled with peripheral neurectomy. The patient was pain free with a maintenance dose of 200 mg carbamazepine daily for about 1 year, after which she elected to undergo stereotactic gamma knife radiosurgery when pain recurred at the external nasal region.
    Matched MeSH terms: Facial Pain/drug therapy
  14. Muniandy S, Yahya HM, Shahar S, Kamisan Atan I, Mahdy ZA, Rajab NF, et al.
    BMJ Open, 2023 Nov 01;13(11):e073323.
    PMID: 37914304 DOI: 10.1136/bmjopen-2023-073323
    INTRODUCTION: Eurycoma longifolia Jack (EL), profoundly recognised as 'Tongkat Ali', is a medicinal herb originating from Southeast Asia. It is commonly used in traditional 'antiageing' treatments to address decreased energy, mood, libido and hormonal imbalances. While the benefits of EL have been extensively studied among the male population, less attention has been given to its effects on women. Menopause can impact the overall well-being of middle-aged women and incorporation of herbal supplements can aid them in managing the menopausal symptoms.

    METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis.

    ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications.

    TRIAL REGISTRATION NUMBER: ACTRN12622001341718.

    Matched MeSH terms: Pain/drug therapy
  15. Mohamad AS, Akhtar MN, Khalivulla SI, Perimal EK, Khalid MH, Ong HM, et al.
    Basic Clin Pharmacol Toxicol, 2011 Jun;108(6):400-5.
    PMID: 21214864 DOI: 10.1111/j.1742-7843.2010.00670.x
    The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.
    Matched MeSH terms: Pain/drug therapy
  16. Ming-Tatt L, Khalivulla SI, Akhtar MN, Mohamad AS, Perimal EK, Khalid MH, et al.
    Basic Clin Pharmacol Toxicol, 2012 Mar;110(3):275-82.
    PMID: 21967232 DOI: 10.1111/j.1742-7843.2011.00804.x
    This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
    Matched MeSH terms: Pain/drug therapy*
  17. Masiran R, Ilias MNA, Yubbu P
    BMJ Case Rep, 2023 Nov 27;16(11).
    PMID: 38011950 DOI: 10.1136/bcr-2023-255187
    A young child was diagnosed with autism spectrum disorder with comorbid attention-deficit/hyperactivity disorder. His hyperactivity, impulsivity and absence of awareness towards danger increased his risk of harm and hence methylphenidate was indicated. Unfortunately, he developed chest pain eight months after the treatment initiation. We then stopped the stimulant and changed his treatment to atomoxetine, after which he no longer had chest pain. In the following illustrated case, we will discuss the cardiac side effect of methylphenidate.
    Matched MeSH terms: Chest Pain/drug therapy
  18. Mani V, Ramasamy K, Abdul Majeed AB
    Food Funct, 2013 Apr 25;4(4):557-67.
    PMID: 23360913 DOI: 10.1039/c3fo30356j
    The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavour that they impart. In the present study, the effect of the total alkaloidal extract from Murraya koenigii leaves (MKA) with respect to anti-inflammatory, analgesic and anti-ulcerogenic effects were evaluated using different experimental animal models. Oral supplementation of MKA at 10, 20 and 40 mg kg(-1) body weight successfully and dose-dependently reduced the formation of oedema induced by carrageenan, histamine and serotonin as well as formaldehyde-induced arthritis. In addition, the extract (10, 20 and 40 mg kg(-1), p.o.) attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by a subplantar injection of formalin in mice. MKA at higher doses (20 and 40 mg kg(-1), p.o) reduced the early phase response induced by formalin as well as reaction time on hot plate models. Interestingly, there was no ulcer score with the ulcerogenic effect of MKA. Moreover, all the doses of MKA (10, 20 and 40 mg kg(-1), p.o) showed promising anti-ulcerogenic activity with protection against acute gastric ulcers induced by ethanol plus hydrochloric acid and aspirin models in a dose dependent manner.
    Matched MeSH terms: Pain/drug therapy
  19. Ling JM, Quah BS, Van Rostenberghe H
    Med J Malaysia, 2005 Jun;60(2):140-5.
    PMID: 16114153
    The objective of this study was to assess the efficacy and safety of oral 30% dextrose during venepuncture in neonates. Neonates admitted in the Special Care Nursery for jaundice from September 200 to January 2001 were recruited for this double-blind randomised controlled trial. The intervention consisted of administration of either 2 ml of oral 30% dextrose or 2 ml of sterile water 2 minutes before venepuncture. The primary outcome measure was the cumulative Neonatal Infant Pain Scale (NIPS) score at 3 minutes after venepuncture and the duration of cry assessed from a videotaped recording. Twenty-six neonates received 30% dextrose and 26 neonates received sterile water. The cumulative NIPS score at 3 minutes (median, IQR) after venepuncture for neonates given 30% dextrose (13, 6.8-21) was significantly (p = 0.03) lower than that for neonates given sterile water (21, 13.8-21). The duration of cry in neonates given 30% dextrose (median 45 sec IQR 1.5-180.8 sec) was significantly (p = 0.03) shorter than that in neonates given sterile water (median 191 sec IQR 52.3-250 sec). No neonates developed diarrhoea, fever or rash during the 24 hour observation period. Both the intra-rater (ICC 0.993 95% CI 0.988-0.996) and inter rater (ICC 0.988 95% CI 0.980-0.993) agreement on the 3-minute NIPS score were good. In conclusion oral 30% dextrose given 2 minutes before venepuncture was effective in reducing neonatal pain following venepuncture. It is a simple, safe and fast acting analgesic and should be considered for minor invasive procedure in term neonates.
    Matched MeSH terms: Pain/drug therapy*
  20. Lee MT, Mackie K, Chiou LC
    Br J Pharmacol, 2023 Apr;180(7):894-909.
    PMID: 34877650 DOI: 10.1111/bph.15771
    The use of opioids in pain management is hampered by the emergence of analgesic tolerance, which leads to increased dosing and side effects, both of which have contributed to the opioid epidemic. One promising potential approach to limit opioid analgesic tolerance is activating the endocannabinoid system in the CNS, via activation of CB1 receptors in the descending pain inhibitory pathway. In this review, we first discuss preclinical and clinical evidence revealing the potential of pharmacological activation of CB1 receptors in modulating opioid tolerance, including activation by phytocannabinoids, synthetic CB1 receptor agonists, endocannabinoid degradation enzyme inhibitors, and recently discovered positive allosteric modulators of CB1 receptors. On the other hand, as non-pharmacological pain relief is advocated by the US-NIH to combat the opioid epidemic, we also discuss contributions of peripheral neuromodulation, involving the electrostimulation of peripheral nerves, in addressing chronic pain and opioid tolerance. The involvement of supraspinal endocannabinoid systems in peripheral neuromodulation-induced analgesia is also discussed. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
    Matched MeSH terms: Pain/drug therapy
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