Time course of degeneration and regeneration of myelinated nerve fibres following chronic loose ligatures of the rat sciatic nerve: can nerve lesions be linked to the abnormal pain-related behaviours?

Abstract

This study of a mononeuropathy of 1-15 weeks (W) duration was induced in rats by setting 4 loose ligatures around the common sciatic nerve. This chronic lesion, in which the continuity of the nerve was maintained, has been introduced as a model for experimental pain. Quantitative analyses of teased nerve fibres and a morphometric analysis of semi-thin transverse sections, were performed and completed by electron microscopic examination. Morphological changes were observed mainly distal, but also proximal, to the ligatures, indicating significant axonopathy with simultaneous degeneration and regeneration. The lesions were analysed in parallel with the time course of the pain-related behaviours. Both were at their maximum 2 weeks after ligature with progressive recovery beginning between W3 and W4. However, the largest fibres had not totally recovered by W15, contrasting with the disappearance of abnormal nociceptive reactions between W8 and W10. Although the damage to unmyelinated fibres is of importance, the abnormal pain-related behaviours seen in these rats appeared to be closely linked to the presence of both degenerative and regenerative changes in the A delta-range fibres, which did not necessarily correspond to initial A delta fibres.

Soft Tissue Repair Capacity after Oxygen-Derived Free Radical-Induced Damage in One Hindlimb of the Rat

“…The alterations in pain sensation (spontaneous pain, m echanical pain, and therm al pain) found after 24 hr of exposure to free radicals are also obtained in anim al models of neuropathic pain [18], inflam m ation [19,20,28,29], and in ju ry [30,31]. The pain behavior in the present model does not appear to be based on neuro pathic injury, because in neuropathic injury the re sulting appearance of pain sensations required more tim e to develop [21,32]. Strikingly, we observed in creased mechanical p ain sensitivity of the contralateral leg in the present experimental model.…”

Differential Implication of Proinflammatory Cytokine Interleukin-6 in the Development of Cephalic versus Extracephalic Neuropathic Pain in Rats

“…The latter model differs markedly from our IoN-CCI cephalic model (loose ligatures of the fibers innervating the vibrissae territory vs transection of fibers innervating adjacent territories in the model of Piao et al). In particular, previous studies showed that, after cutting a nerve, most of degenerating cells are smalldiameter DRG neurons at the origin of unmyelinated fibers (Janig and McLachlan, 1984), whereas the vast majority of degenerating neurons after CCI are large-diameter cells at the origin of myelinated fibers (Guilbaud et al, 1993). Consequently, lesion-induced signals emitted by primary afferent fibers very probably differ in the model of Piao et al (2006) and the IoN-CCI model used here.…”

“…Indeed, the difference between the effects of ligation on the two nerves is more probably related to the presence of a higher density of myelinated fibers in the IoN (50%) than in the SN (20%) (Young, 1977). Guilbaud et al (1993) clearly showed that myelinated fibers are the most vulnerable to CCI. In additional support of this interpretation, ATF3, which is considered as a marker of neuronal response to injury (Hai and Hartman, 2001) and is essentially expressed by medium to large neurons (Obata et al, 2003;Tsuzuki et al, 2003) from which originate myelinated fibers (Lazarov, 2002), was also found to exhibit a more robust and faster upregulation after IoN-CCI compared with SN-CCI.…”

Influence of Breaching the Connective Sheaths of the Donor Nerve on Its Myelinated Sensory Axons and on Their Sprouting into the End-to-Side Coapted Nerve in the Rat

“…Namely, subepineurial demyelination, degeneration, and axonal sprouting were found also after stripping the vessels from the epineurium, as well as after perineurial windowing or in experimental entrapment neuropathies with chronic loose ligatures. 42,45,67 However, once the axon sprouting from the donor nerve is enhanced, the ingrowth of sprouting axons into the recipient nerve depends upon the soluble and insoluble factors provided by the Schwann cells from the recipient nerve. 47,60 Therefore, it is possible that even the small holes created by needle penetration and sutures through the epineurium during the end-to-side repair are sufficient to enhance growth factor diffusion or Schwann cell migration in the early postoperative period.…”