Time course of degenerative and regenerative changes in the dorsal horn in a rat model of peripheral neuropathy

Abstract

The time course of histochemical changes in the dorsal horn of rats subjected to an experimental peripheral neuropathy has been examined. Qualitative and quantitative analyses of the changes in dorsal horn staining were made for soybean agglutinin (SBA)-binding glycoconjugates, the soluble lectins RL-14.5 and RL-29, the growth-associated protein (GAP)-43, and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). These analyses were made at various time points after chronic constriction of the sciatic nerve. Quantitative analysis indicated that staining density increased in the normal territories stained for SBA-binding glycoconjugates, RL-14.5, RL-29, and GAP-43 on the neuropathic side compared with the control side. In addition, there was an extension of the territories stained for SBA-binding glycoconjugates and RL-29 ipsilateral to the injury. The peak increases occurred at 14 or 28 days, followed by a decrease toward control levels by 70 days. In contrast, the staining density for SP in the ipsilateral dorsal horn decreased at 3 and 5 days and reached a peak decrease at 14 days. Then, the staining for SP returned toward control values. The staining for CGRP was unchanged at all time points examined. Dorsal rhizotomies ipsilateral to the nerve injury in neuropathic rats indicated that the increases in staining were attributable to changes in primary afferent neurons. These data suggest that peripheral neuropathy causes complex degenerative and regenerative changes in the central branches of primary afferent neurons. The associated synaptic reorganization may contribute to the sensory abnormalities that accompany peripheral neuropathy.

Altered antinociceptive efficacy of tramadol over time in rats with painful peripheral neuropathy

“…Since CNS changes occur over time during disease or injury progression, it is likely that responses to a given drug will change over time as well (Cameron et al, 1997;Eaton et al, 1999;Goff et al, 1998;Maihofner et al, 2003). The utility of testing drugs at different times following injury would be not only to indicate which treatments may be of use at either early or late times (or both) after nerve injury but also to pharmacologically point out changes in a drug-related mechanism.…”

“…Alternatively, a change in drug efficacy may be due to alterations in a drugrelated mechanism over time, such a decrease in receptor function over time due to continuous exposure to the drug (Bailey and Connor, 2005). Data from rat models of chronic neuropathic pain have demonstrated nerve injury-related changes in CNS receptors and neuropeptides over time (Cameron et al, 1997;Goff et al, 1998). It is presumed that analgesics tested at different times in such rats will show an alteration in efficacy because of the neuropathy-related changes.…”

Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist

“…This conclusion is supported by the observation that NK-1 receptors are increased following nerve injury (Aanonsen et al, 1992). Furthermore, Cameron et al (1997) have reported a significant correlation between thermal allodynia and maximal changes in substance P and NK-1 receptor expression.…”

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

“…The integrated optical density (IOD) was determined using Image Pro Plus v 3.0. Integrated optical density is a previously used methodology (Garrison et al, 1994;Cameron et al, 1997) that is determined by averaging the intensity of fluorescence × area of labeling within a defined immunofluorescence intensity threshold. The intensity threshold was set to exclude nonspecific background fluorescence and applied to all sections analyzed.…”