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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Are Headaches Taking Your Life Hostage and Preventing You From Living to Your Fullest Potential? Are you tired of being given the run around by doctors who tell you that your headaches or migraines are psychological or that they have no cause that can be treated? Are you sick of calling in sick because you woke up with a headache so bad that you can barely think or see straight?