Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat

Shim, Beom; Ringkamp, Matthias; Lambrinos, George L.; Hartke, Timothy V.; Griffin, John W.; Meyer, Richard A.

doi:10.1016/j.pain.2006.08.023

Cited by 34 publications

(26 citation statements)

References 36 publications

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“…Differences in preparation (in vitro versus in vivo) or recording period for spontaneous activity (2 min [present study] versus 5 min [Wu et al, 2001]) may account for this discrepancy. Shim et al (2007) reported an enhancement of activity-dependent slowing of CV and supranormal CV in uninjured nerves following L5 SNL, providing further evidence that the excitability of uninjured primary afferent fibers can be altered in the presence of injured afferents. We did not analyze activity-dependent slowing of CVs in this study; however, given that the fibers appeared to be changing categories, we compared the distribution of CVs to provide some assurance that we were studying comparable Aδ-and C-fiber populations in the SNL and naïve groups.…”

Section: Physiological Correlates To Behavioral Changesmentioning

confidence: 66%

Plasticity in intact Aδ- and C-fibers contributes to cold hypersensitivity in neuropathic rats

Zhou

Kochukov

et al. 2007

Neuroscience

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Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 °C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous Aδ-and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the Aδ-but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in Aδ-fibers: the percentage of L4 cold sensitive Aδ-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive Aδ-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 Aδ-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both Aδ-and C-uninjured fibers, but Aδ fibers appear to provide a major contribution to cold hypersensitivity in neuropathic rats.Keywords peripheral neuropathy; sensitization; TRPA1; TRPM8; neuropathic pain; cold allodynia Cold hypersensitivity is a striking feature in patients (Wahren and Torebjörk, 1992;Ochoa and Yarnitsky, 1994;Bowsher and Haggett, 2005), and animals (Choi et al., 1994;Vissers and Meert, 2005) with peripheral nerve injuries. The mechanisms underlying enhanced sensitivity to cold remain unclear. Evidence suggests that receptors expressed on peripheral sensory fibers contribute to the sensation of cold pain. For example, it is well documented that peripheral Aδ-and C-fibers are activated by non-painful cooling and a subpopulation of nociceptors is excited by noxious cold (Dubner et al., 1975;Georgopoulos, 1976;Leem et al., 1993a;Simone and Kajander, 1997). In agreement with these physiological findings, two cold-activated ion channels, transient receptor potential M8 and A1 (TRPM8 and TRPA1, respectively) have been shown to be expressed by dorsal root ganglion (DRG) cells (Reid and Flonta, 2001a,b; *Corresponding author. Tel: +1-409-772-...

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Section: Physiological Correlates To Behavioral Changesmentioning

confidence: 66%

Plasticity in intact Aδ- and C-fibers contributes to cold hypersensitivity in neuropathic rats

Zhou

Kochukov

et al. 2007

Neuroscience

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“…Published studies in mice have described pain behavior after ligation of the L5 spinal nerve, with [8,30] or without [20,22,28,33] ligation of the L6 nerve. Our finding of only a minor contribution of the mouse L5 spinal nerve to the sciatic nerve predicts that L5 ligation will minimally affect the population of afferents going to the foot or sciatic nerve in the thigh.…”

Section: Consideration Of the Published Literature In The Context Of mentioning

confidence: 99%

Species and strain differences in rodent sciatic nerve anatomy: Implications for studies of neuropathic pain

Rigaud

Gemes

Barabas

et al. 2008

Pain

254

235

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Hindlimb pain models developed in rats have been transposed to mice, but assumed sciatic nerve neuroanatomic similarities have not been examined. We compared sciatic nerve structural organization in mouse strains (C57BL/6J, DBA/2J, and B6129PF2/J) and rat strains (Wistar, Brown Norway, and Sprague-Dawley). Dissection and retrograde labeling showed mouse sciatic nerve origins predominantly from the third lumbar (L3) and L4 spinal nerves, unlike the L4 and L5 in rats. Proportionate contributions by each level differed significantly between strains in both mice and rats. Whereas all rats had six lumbar vertebrae, variable patterns in mice included mostly five vertebrae in DBA/2J, mostly six vertebrae in C57BL/6J, and a mix in B6129PF2/J. Mice with a short lumbar vertebral column showed a rostral shift in relative contributions to the sciatic nerve by L3 and L4. Ligation of the mouse L4 nerve created hyperalgesia similar to that in rats after L5 ligation, and motor changes were similar after mouse L4 and rat L5 ligation (foot cupping) and after mouse L3 and rat L4 ligation (flexion weakness). Thus, mouse L3 and L4 neural segments are anatomically and functionally homologous with rat L4 and L5 segments. Neuronal changes after distal injury or inflammation should be sought in the mouse L3 and L4 ganglia, and the spinal nerve ligation model in mice should involve ligation of the L4 nerve while L3 remains intact. Strain-dependent variability in segmental contributions to the sciatic nerve may account in part for genetic differences in pain behavior after spinal nerve ligation.

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“…In a case of neuropathic pain, it is presumed that a nerve injury leads to persistent alterations in the properties of adjacent uninjured, unmyelinated fibers because of changes in expression of ion channels responsible for the membrane excitability (Gold et al, 2003;Shim et al, 2007). In the effort to develop effective treatments for atypical orofacial pain, it is important to establish an appropriate model, and to investigate the exact mechanisms of ectopic heat hyperalgesia induced by local inflammation in the orofacial region.…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor Contribution via Transient Receptor Potential Vanilloid 1 to Ectopic Orofacial Pain

Shinoda¹,

Asano²,

Omagari³

et al. 2011

J. Neurosci.

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It is well known that oral inflammation causes tenderness in temporomandibular joints or masseter muscles. The exact mechanism of such an orofacial ectopic hyperalgesia remains unclear. Here, we investigated the functional significance of interaction of nerve growth factor (NGF) and transient receptor potential vanilloid 1 (TRPV1) in relation to heat hyperalgesia in the whisker pad skin caused by complete Freund's adjuvant (CFA) injection into the lower lip. CFA injection induced heat hyperalgesia of the ipsilateral whisker pad skin. Moreover, it leads to enhancement of spontaneous activity and heat responses in trigeminal ganglion (TG) neurons that was elicited by heat stimulation of the whisker pad skin. The heat hyperalgesia was dose-dependently reversed by intraperitoneal TRPV1 antagonist administration, also diminished by neutralizing anti-NGF antibody administration into the lower lip and intraganglionic administration of K252a, a tyrosine kinase receptor inhibitor. Nerve fibers in bundle of mandibular nerve and TG neurons that innervates the whisker pad skin and lower lip both expressed labeled NGF, which was administrated into the lower lip. Moreover, the NGF concentrations in ophthalmic-maxillary and mandibular divisions of the TG increased after CFA injection into the lower lip. The number of TRPV1-positive neurons that innervates the whisker pad skin and lower lip was increased after CFA injection into the lower lip, and this increase was annulled by anti-NGF administration. The present findings suggest that inflammation in the lower lip induces release of NGF that regulates TRPV1 expression in TG neurons. This TRPV1 overexpression may underlie ectopic heat hyperalgesia in the whisker pad skin.

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Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat

Cited by 34 publications

References 36 publications

Plasticity in intact Aδ- and C-fibers contributes to cold hypersensitivity in neuropathic rats

Plasticity in intact Aδ- and C-fibers contributes to cold hypersensitivity in neuropathic rats

Species and strain differences in rodent sciatic nerve anatomy: Implications for studies of neuropathic pain

Nerve Growth Factor Contribution via Transient Receptor Potential Vanilloid 1 to Ectopic Orofacial Pain

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