Opioid system

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The endogenous opioid system is also dysregulated following nerve injury. Evidence supports a loss of m-opioid receptors in the DRG137 and in the spinal cord following nerve injury.40,138139 Spinal opioid receptors are localized predominantly on the presynaptic terminals of primary afferents in the superficial dorsal horn138 and therefore this may reflect degeneration of primary afferent neurons. Additionally, increased cholecystokinin (CCK) mRNA synthesis by DRG neurons140 and increased expression of the CCKB receptor in the superficial dorsal horn following peripheral axotomy may potentially decrease the anti-nociceptive effects of opioids due to opioid antagonistic properties of CCK.141 These changes may all contribute to the reduced potency of peripherally or spinally delivered opioids in neuropathic pain (Figure 1.7).142

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