Involvement of substance P and calcitonin gene-related peptide in development and maintenance of neuropathic pain from spinal nerve injury model of rat.
Recently, it has been suggested that uninjured primary sensory neurons contribute to neuropathic pain induced by peripheral nerve injury. However, there is lack of evidences of roles of normal pain transmitting substances such as substance P and calcitonin gene-related peptide (CGRP) in neuropathic pain. Whether substance P and CGRP have a role in spinal nerve-injured neuropathic pain model was tested. Male rats were subjected to L5 and L6 spinal nerve transection (SNT), and mechanical hyperalgesia was evaluated by measuring paw withdrawal threshold (PWT). SNT induced a persistent PWT decrease, a sign of neuropathic pain. Lidocaine was soaked on spinal nerves or intrathecally injected 10 min before SNT to block neuronal discharges caused by the injury, and L703,606 (NK1 receptor antagonist) and CGRP8-37 (CGRP receptor antagonist) were intrathecally injected into the rats to block actions of substance P and CGRP released from central nerve terminals in the spinal cord by injury discharges. The treatments with lidocaine, L703,606 and CGRP8-37 delayed the onset of neuropathic pain by 1-4 days, compared with the saline-treated rats. After neuropathic pain was established, intrathecal injections of L703,606 and CGRP8-37 significantly mitigated mechanical hyperalgesia for 20 min. These results suggest that substance P and CGRP are involved in the development and maintenance of neuropathic pain and that these peptides from the central terminals of intact sensory neurons contribute to the maintenance of peripheral nerve injury-induced neuropathic pain.
Lee
Seo Eun
SE
Department of Physiology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, South Korea. selee63@hanyang.ac.kr
Kim
Jin-Hyuk
JH
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D010147:Pain Measurement / Q000379:methods; D010446:Peptide Fragments / Q000627:therapeutic use; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves; D013373:Substance P / Q000502:physiology*; D013997:Time Factors
D000779:Anesthetics, Local; D010446:Peptide Fragments; D011812:Quinuclidines; C058636:calcitonin gene-related peptide (8-37); C076851:L 703606; D013373:Substance P; D008012:Lidocaine; D015740:Calcitonin Gene-Related Peptide