Pain
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Although regulation of nociceptive processes in the dorsal horn by deep brain structures has long been established, the role of cortical networks in pain regulation is minimally explored. The medial prefrontal cortex (mPFC) is a key brain area in pain processing that receives ascending nociceptive input and exerts top-down control of pain sensation. We have shown critical changes in mPFC synaptic function during neuropathic pain, controlled by endocannabinoid (eCB) signaling. ⋯ Spared nerve injury reduced the mechanical threshold to induce action potential firing of dorsal horn wide-dynamic-range neurons, but this was reversed in rats by WIN in the chronic phase of SNI and by mPFC injection of AM4113 in the early phase of SNI. Elevated dorsal root ganglion neuronal activity after injury was also diminished in rats by mPFC injection of AM4113, potentially by reducing antidromic activity and subsequent neuronal inflammation. These findings suggest that depending on the phase of the pain condition, both blocking and activating CB1 receptors in the mPFC can regulate descending control of pain and affect both dorsal horn neurons and peripheral sensory neurons, contributing to changes in pain sensitivity.
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Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain. ⋯ Gabapentinoid use had greater odds of less-than-daily pain post-prescription, in a dose-dependent manner. Thus, GABA use was associated with a larger reduction in chronic pain than opioids, with a larger effect at higher GABA dosage. Future research is needed on functional outcomes in patients with chronic pain prescribed GABA or opioids.