Decreases in spinal cord endorphin levels in chronic pain

[Wise Young]

• Smith RR, Martin-Schild S, Kastin AJ and Zadina JE (2001). Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain after nerve injury. Neuroscience. 105 (3): 773-8. Summary: Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is an endogenous morphine-like substance that binds to the &mgr;-opioid receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity (LI) is present in the superficial layers of the dorsal horn in the spinal cord and in primary afferents, suggesting a role for this peptide in pain transmission. To determine whether spinal endomorphin-2-LI is altered in an animal model of chronic pain, the left sciatic nerve of Swiss Webster and ICR mice was ligated in a modified Seltzer model of nerve injury. Changes in endomorphin-2-LI were assessed by immunocytochemistry at 2, 4 and 14 days after nerve injury. The side of the spinal cord ipsilateral to the nerve injury exhibited a dramatic decrease in endomorphin-2-LI relative to the contralateral side and to control animals. The change was restricted to the medial dorsal horn in the lumbar segments innervated by the sciatic nerve. Substance P-LI showed a small decrease, while calcitonin gene-related peptide-LI was unchanged. Both thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal latencies, and decreased endomorphin-2-LI were observed within 2 days of injury and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2-LI during the development of chronic pain is consistent with the loss of an inhibitory influence on pain transmission.These results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11516840>

[David Berg]

This study measures endorphin levels, but I'm a little curious if there's any way they could measure whether or not the endorphin receptors are functioning. I'm inclined to think there isn't. If the receptors aren't functioning, then the endorphins are merely "formerly inhibitory substances." This comes to mind because there are instances where endorphins don't seem to do any good.

David Berg