Chromic gut suture reduces calcitonin-gene-related peptide and substance P levels in the spinal cord following chronic constriction injury in the rat

Abstract

The chronic constriction injury (CCI) is an animal model of an experimental peripheral neuropathy. In this model, a mononeuropathy is produced by loosely ligating the left sciatic nerve of the rat with chromic gut suture (Bennett and Xie 1988). Maves et al. (1993) have proposed that chemical constituents of chromic gut suture influence the behavioral changes of rats with the CCI. Considering their results, we became interested in evaluating whether the type of suture material used to produce the CCI also affected spinal levels of calcitonin-gene-related peptide immunoreactivity (CGRP-ir) and substance P immunoreactivity (SP-ir), peptides that are associated with small primary afferent neurons. Using methods of radioimmunoassay (RIA), we measured levels of CGRP-ir and SP-ir in the dorsal quadrants of approximately the lumbar 4-5 (L4-L5) spinal segments of rats with a CCI induced using polyglactin (Vicryl), plain gut, or chromic gut suture. We observed bilateral decreases in CGRP-ir and SP-ir 60 days after a CCI induced with chromic gut suture, but no changes in peptide levels after a CCI induced with either polyglactin or plain gut suture. These results suggest two possibilities: (1) chromic gut suture, when used to produce the CCI, has more than just a constrictive effect on the sciatic nerve, and/or (2) different suture materials produce changes in CGRP-ir and SP-ir with a differential time-course. Our experiments are unable to distinguish between these two possibilities.

Schwann Cell Proliferation and Macrophage Infiltration Are Evident at Day 14 after Painful Cervical Nerve Root Compression in the Rat

“…It should also be noted that unilateral application of chromic gut material alone (Cg) is sufficient to induce bilateral upregulation of substance P in the DRG, suggesting a potential diffusion effect of the inflammatory material of the chromic gut sutures and/or central sensitization. However, nerve root injury has also been reported to reduce substance P when injury-induced behavioral hypersensitivity was produced (Hubbard et al, 2008a;Kobayashi et al, 2004aKobayashi et al, , 2005Noguchi et al, 1995;Rothman et al, 2005;Xu et al, 1996). For example, we have observed decreased substance P in the dorsal horn of the spinal cord and DRG at 7 days following nerve root compression dependent on the presence of mechanical allodynia (Hubbard et al, 2008a,b) and also for the same compression injury used in the current study (Rothman et al, 2005).…”

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

“…A role for substance P in neuropathic pain is implicated by studies demonstrating alterations in substance P-like immunoreactivity following nerve injury. CCI has been found to produce decreases in substance P-like immunoreactivity in the ipsilateral spinal cord dorsal horn (Cameron et al, 1991;Garrison et al, 1993;Xu et al, 1996) and DRG (Munglani et al, 1995) for up to 60 days following the nerve injury, although this effect is dependent on the type of ligatures used . Nerve injury can also lead to increases in substance P mRNA in the ipsilateral spinal cord dorsal horn (Delander et al, 1997), as well as increases in the level of pre-protackykinin A mRNA, a precursor of substance P, in the DRG (Marchand et al, 1994;Noguchi et al, 1994).…”

Chemical and mechanical nerve root insults induce differential behavioral sensitivity and glial activation that are enhanced in combination

“…As such, lumbar radiculopathy models have also separated these injury components to investigate their effects on behavioral hypersensitivity (Olmarker et al, 1993;Maves et al, 1993;Kawakami et al, 1994a,b;Kajander et al, 1996;Colburn et al, 1999;Hashizume et al, 2000;Hou et al, 2003;Murata et al, 2004;Winkelstein and DeLeo, 2004;Hubbard and Winkelstein, 2005). Though radicular pain models implement ligation with chromic gut to simultaneously apply compression and chemical irritation in low back pain (Maves et al, 1993;Kawakami et al, 1994a,b;Kajander et al, 1996;Xu et al, 1996;Colburn et al, 1999;Hashizume et al, 2000;Winkelstein and DeLeo, 2004;Robinson and Meert, 2005), mechanistic information for cervical disc herniation is limited.…”