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Knee osteoarthritis is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture analgesia.
The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in electroacupuncture analgesia. The 5-HT7receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA).
In the present study, we found that electroacupuncture significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7receptor agonist AS-19 mimicked the analgesic effect of electroacupuncture, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to electroacupuncture intervention prevented its anti-allodynic effect.
In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to electroacupuncture intervention blocked the electroacupuncture effect on pain hypersensitivity.
Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in electroacupuncture-mediated inhibition of chronic pain in a mouse model of knee osteoarthritis.
Reference: https://pubmed.ncbi.nlm.nih.gov/34602973/