Abstract
Chronic neuropathic pain is a debilitating condition that remains poorly treated by current medications. Preclinical studies have indicated that cannabinoid receptor agonists have analgesic efficacy in neuropathic pain models, but this is accompanied by undesirable side effects. In recent years, novel strategies targeting the endogenous cannabinoid system have emerged, which are being mooted as safer alternatives. A recent clinical trial, however, has demonstrated that a new endocannabinoid modulator is ineffective against osteoarthritic pain, despite exhibiting efficacy during the preclinical stage. Further basic and clinical work is needed to resolve this disparity.
Highlights
Chronic neuropathic pain is a debilitating condition that remains poorly treated by current medications
Preclinical studies have indicated that cannabinoid receptor agonists have analgesic efficacy in neuropathic pain models, but this is accompanied by undesirable side effects
Endocannabinoids are present in multiple pain-modulating regions throughout the CNS, including the periaqueductal gray (PAG), rostral ventral medulla (RVM) and spinal cord dorsal horn, where their levels are enhanced by acute nociceptive stimuli and stress (e.g., Walker et al, 1999; Hohmann et al, 2005)
Summary
Chronic neuropathic pain is a debilitating condition that remains poorly treated by current medications. Preclinical studies have indicated that cannabinoid receptor agonists have analgesic efficacy in neuropathic pain models, but this is accompanied by undesirable side effects. Inhibition of these degradative enzymes is thought to enhance endocannabinoids where they are produced on demand, resulting in more localized receptor activation compared to globally acting exogenous agonists.
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