A new study published in The Journal of Pain finds that cannabidiol (CBD) can reduce nerve pain and improve memory by activating spinal PPARγ and 5-HT1A receptors.
Researchers evaluated the effects of both acute and repeated doses of CBD in female mice with nerve injury-induced neuropathic pain. The study found that CBD significantly reduced tactile allodynia and spontaneous pain. The partial antiallodynic effect of pioglitazone, a PPARγ agonist, was blocked when a PPARγ antagonist was used, indicating the receptor’s key role in pain relief.
Similarly, CBD’s effect was diminished when either a PPARγ antagonist or a 5-HT1A receptor antagonist was administered, but not when a PPARα antagonist was used. When both antagonists were given together, the pain-relieving effects of CBD were entirely blocked.
The study also found that nerve injury increased PPARγ expression in the spinal cord and dorsal root ganglia, and repeated CBD treatment amplified this upregulation. Additionally, repeated intrathecal administration of CBD lowered levels of pain markers (ERK, p-ERK, p38MAPK, and p-p38MAPK), restored levels of the anti-inflammatory cytokine IL-10, and improved cognitive deficits caused by nerve injury.
The findings suggest that CBD’s pain-relieving effects are at least partially mediated through spinal PPARγ and 5-HT1A receptors and that it may also offer cognitive benefits in the context of chronic nerve pain. The researchers say these insights could support new therapeutic strategies for treating neuropathic pain and its related comorbidities.
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