Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats

Abstract

Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicates that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 dpi when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia group had extensive overlap of the 2 c fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are post-injury periods when exercise can be deleterious.

Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation

“…exercise initiated after injury) in human chronic pain populations are mixed, mainly due to differences in type of pain, type of exercise and exercise intensity [40; 55; 67; 72; 95]. In contrast, rodent studies employing therapeutic exercise uniformly show robust analgesic effects in a variety of persistent pain models and using a variety of exercise intensities [4; 9; 11; 18–24; 34; 35; 41; 54; 63; 69; 81; 82; 93; 102; 103; 112; 132]. Importantly, none of these studies assessed stress-related outcomes such as plasma corticosterone despite employing forced running paradigms that can be highly stressful [28; 36; 48; 62; 74; 80; 88; 89; 92].…”

The Impact of Exercise in Rodent Models of Chronic Pain

“…Under these conditions, the vast majority of studies (36 or 90%) reported that at least some form of therapeutic exercise was effective in reducing or reversing mechanical hypersensitivity. While three of the four studies showing no beneficial effect of therapeutic exercise on mechanical hypersensitivity initiated exercise 8 or more days after injury [ 92 , 98 , 118 ], other studies using similar delays in initiation of exercise were effective [ 87 , 91 •, 114 ••, 116 , 119 , 120 ]. Similarly, while two of the four studies showing no beneficial effect of therapeutic exercise on mechanical hypersensitivity used voluntary exercise paradigms [ 98 , 101 ], other studies using voluntary exercise were effective [ 87 , 97 , 99 ••, 100 ••].…”

Chromaffin cell transplantation for neuropathic pain after spinal cord injury: a report of two cases

“…atrophic changes versus increases in volume) and may provide substrates for the underlying neural mechanisms in the development of NP. 16,17 Anticonvulsants remain the most studied and supported pharmacotherapy for NP post-SCI. Antidepressants likely showed reduction in pain only among those with comorbid depression.…”