European journal of pain : EJP
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Drugs activating the mu opioid receptor are routinely used to treat severe acute and chronic pain. Unfortunately, side effects including nausea, constipation, respiratory depression, addiction and tolerance can limit clinical utility. In contrast, kappa opioid receptor (KOPr) agonists, such as Salvinorin A (SalA), have analgesic properties with little potential for abuse. ⋯ Salvinorin A and the novel analogue β-THP Salvinorin B show analgesic effects in the tail-withdrawal and formalin assays. They reduce oedema and decrease neutrophil infiltration into inflamed tissue, and suppress mechanical and cold allodynia in paclitaxel-induced neuropathic pain.
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γ-Aminobutyric acid (GABA) type A receptors (GABAARs) locate at both synaptic and extrasynaptic membrane, which generate phasic and tonic inhibition, respectively. In spinal cord dorsal horn, the phasic inhibition produced by transient activation of synaptic GABAARs plays an important role in the gating control over nociceptive conveyance. Although extrasynaptic GABAARs that contain α5 subunits (α5-GABAARs) are also detectable in spinal dorsal horn, much less is known about the function of these receptors. ⋯ Tonic inhibition generated by α5-GABAARs is important for information processing. However, whether and how α5-GABAARs regulate the conveyance of nociceptive signals in spinal cord is largely unknown. Here, we revealed a negative control by α5-GABAARs over nociceptive transmission and plasticity.