Pain
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Chronic neuropathic pain may be caused, in part, by loss of inhibition in spinal pain processing pathways due to attenuation of local GABAergic tone. Nociception and nocifensive behaviors are reduced after enhancement of tonically activated extrasynaptic GABAAR-mediated currents by agonist ligands for δ subunit-containing GABAARs. However, typical ligands that target δ subunit-containing GABAARs are limited due to sedative effects at higher doses. ⋯ Moreover, 2-261 reversed thermal hyperalgesia and partially reversed tactile allodynia in the gp120 model of HIV-related neuropathic pain. The effects of 2-261 likely required interaction with the α4β3δ GABAAR because 2-301, a close structural analog of 2-261 with limited extrasynaptic receptor efficacy, was not active. Thus, 2-261 may produce pain relief with diminished side effects through selective modulation of β2/3-subunit-containing extrasynaptic GABAARs.
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Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis that interacts with the serotonin (5-HT)1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact on models of neuropathic pain are unknown. First, using in vivo single-unit extracellular recordings in rats, we demonstrated that acute intravenous (i.v.) increasing doses of CBD (0.1-1.0 mg/kg) decreased the firing rate of 5-HT neurons in the dorsal raphe nucleus, which was prevented by administration of the 5-HT1A antagonist WAY 100635 (0.3 mg/kg, i.v.) and the TRPV1 antagonist capsazepine (1 mg/kg, i.v.) but not by the CB1 receptor antagonist AM 251 (1 mg/kg, i.v.). ⋯ Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Antiallodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), whereas the anxiolytic effect was blocked only by WAY. Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
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Catechol-O-methyltransferase (COMT) regulates extracellular catecholamines. A widely studied COMT single nucleotide polymorphism (rs4680) changes the translated amino acid from valine to methionine (Val158Met); the polymorphism has been shown to influence opioid use. The aims of this study were to investigate the influence of COMT Val158Met on the likelihood and dose of opioid use in adults with chronic pain. ⋯ No significant association was observed between morphine equivalent dose and genotype under the additive model; however, a significant association was observed under the codominant model (P = 0.0496). A post hoc comparison demonstrated that the Val/Met (P = 0.019) and Met/Met (P = 0.043) genotypes used greater morphine equivalent dose compared with the Val/Val genotype. This study extends key knowledge about the influence of the Met/Met genotype and Met allele on opioid use in adults with chronic pain.
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The aim of this work was to quantify the prevalence and years lived with disability (YLDs) caused by low back pain (LBP) in China from 1990 to 2016. Data from the GBD 2016 (Global Burden of Diseases, Injuries, and Risk Factors Study 2016) were used. We analyzed the age-sex-province-specific prevalence and YLDs for LBP of 33 provinces/regions in China. ⋯ The prevalence and YLDs rate for LBP slightly decreased from 1990 to 2016 in China; however, the total individuals and YLDs increased. Low back pain still ranks as the second leading cause of YLD burden disease in China. Considerable attention should be paid for LBP, especially in the female population.
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The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. ⋯ Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.