Rr. Smith et al., Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain after nerve injury, NEUROSCIENC, 105(3), 2001, pp. 773-778
Nerve injury often leads to chronic, sometimes excruciating, pain. The mech
anisms contributing to this syndrome include neurochemical plasticity in ne
urons involved in the earliest stages of pain transmission. Endomorphin-2 (
Tyr-Pro-Phe-Phe-NH2) is an endogenous morphine-like substance that binds to
the mu -opioid receptor with high affinity and selectivity. Endomorphin-2-
like immunoreactivity (LI) is present in the superficial layers of the dors
al 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 ne
rve injury. Changes in endomorphin-2-LI were assessed by immunocytochemistr
y at 2, 4 and 14 days after nerve injury. The side of the spinal cord ipsil
ateral to the nerve injury exhibited a dramatic decrease in endomorphin-2-L
I 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 evide
nced by significantly decreased paw withdrawal latencies, and decreased end
omorphin-2-LI were observed within 2 days of injury and were most pronounce
d at 2 weeks after injury. The decrease in endomorphin-2-LI during the deve
lopment of chronic pain is consistent with the loss of an inhibitory influe
nce on pain transmission.
These results provide the first evidence that reduction of an endogenous op
ioid in primary afferents is associated with injury-induced chronic pain. P
ublished by Elsevier Science Ltd on behalf of IBRO.