Calcitonin gene-related peptide, substance P and protein gene product 9.5 immunoreactive axonal fibers in the rat footpad skin following partial sciatic nerve injuries.
Chronic constriction injury (CCI) and partial ligation (PSNL) of the sciatic nerve induce a similar neuropathic pain syndrome in rats. We examined calcitonin gene-related peptide (CGRP), substance P (SP) and protein gene product (PGP) 9.5 immunoreactive (IR) axons in the footpad skin after the two types of injury. Four and 14 days after CCI, CGRP- and SP-IR axons in the ipsilateral footpad skin disappeared in most rats, but in one third, sparse CGRP- and SP-IR fibers remained. PGP-IR axons dramatically decreased, but some thick fiber fascicles appeared. At the ultrastructural level, these PGP-IR thick fiber fascicles were characterized as unmyelinated axons surrounded by non-IR Schwann cells. Some of these axons were swollen and irregular in shape. In contrast, 4 days after PSNL, CGRP-, SP-, and PGP-IR axons in the ipsilateral footpad skin were present, though significantly reduced in density, in all rats, and by 14 days all IR fiber densities in the footpad skin partially recovered. The loss of CGRP and SP axons in the footpad skin of the CCI model suggests that sensory nerves containing neuropeptides are not essential in transducing stimuli applied to the footpad skin into neuropathic pain, but the abnormal PGP-IR unmyelinated axons in thick fiber fascicles might play a role. The partial loss and rapid recovery of IR axons in the footpad skin after PSNL shows that the two injury models, causing similar behaviors, are associated with very different patterns of cutaneous innervation at the time when the pain syndrome is well developed.
Department of Physiology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6.
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D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D005528:Foot / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009409:Nerve Crush / Q000009:adverse effects; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012867:Skin / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
D013373:Substance P; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide