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Glial cell line‐derived neurotrophic factor‐mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain
Author(s) -
Kimura M,
Sakai A,
Sakamoto A,
Suzuki H
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13073
Subject(s) - glial cell line derived neurotrophic factor , locus coeruleus , neuropathic pain , yohimbine , neurotrophic factors , medicine , allodynia , hyperalgesia , nociception , anesthesia , spinal cord , pharmacology , analgesic , norepinephrine , neuroscience , endocrinology , central nervous system , antagonist , dopamine , receptor , psychology , psychiatry
Background and Purpose The locus coeruleus ( LC ) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line‐derived neurotrophic factor ( GDNF ), a well‐established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC . Experimental Approach Rats with chronic constriction injury ( CCI ) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α 2 ‐adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF ‐mediated analgesia. The MEK inhibitor U 0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF . Key Results Both mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF . The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U 0126 into the LC . Conclusions and Implications GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.