Involvement of peripherally released substance P and calcitonin gene-related peptide in mediating mechanical hyperalgesia in a traumatic neuropathy model of the rat.
We hypothesized that neuropeptides released from the peripheral terminals of primary afferents play an important role in mechanical hyperalgesia after peripheral nerve injury. Nerve injury was performed on rats with lumbar 5 spinal nerve lesion (L5 SNL), which was preceded by L5 dorsal rhizotomy (L5 DR) to avoid the potential central effects induced by L5 SNL through the L5 dorsal root. L5 DR produced a short-lasting (<6 days) decrease in paw withdrawal threshold (PWT) while the following L5 SNL produced a persistent (>42 days) PWT decrease. When intraplantar injection to the affected hind paw was given immediately before L5 SNL, antagonists for both neurokinin 1 (NK1) and calcitonin gene-related peptide 1 (CGRP1) receptors delayed the onset of the PWT decrease for 2-4 days. However, when the same injection was given after L5 SNL, CGRP1, but not NK1, receptor antagonist reversed the decreased PWT for 105 min. It is suggested that peripherally released neuropeptides contribute to the generation of neuropathic pain, with substance P and CGRP contributing to its induction phase, but only CGRP to its maintenance phase.
Jang
Jun Ho
JH
Department of Physiology, Brain Research Institute, and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, South Korea.
Nam
Taick Sang
TS
Paik
Kwang Se
KS
Leem
Joong Woo
JW
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D008161:Lumbosacral Region / Q000293:injuries; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019051:Rhizotomy / Q000379:methods; D013119:Spinal Cord Injuries / Q000150:complications*; D018709:Statistics, Nonparametric; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors
D010446:Peptide Fragments; D010880:Piperidines; C058636:calcitonin gene-related peptide (8-37); C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide