Effect of Treadmill Exercise on Serotonin Immunoreactivity in Medullary Raphe Nuclei and Spinal Cord Following Sciatic Nerve Transection in Rats

Abstract

The serotoninergic system modulates nociceptive and locomotor spinal cord circuits. Exercise improves motor function and changes dopaminergic, noradrenergic, and serotonergic central systems. However, the direct relationship between serotonin, peripheral nerve lesion and aerobic treadmill exercise has not been studied. Using immunohistochemistry and optic densitometry, this study showed that the sciatic nerve transection increased the serotoninergic immunoreactivity in neuronal cytoplasm of the magnus raphe nuclei of trained and sedentary rats. In the dorsal raphe nucleus the increase only occurred in sedentary-sham-operated rats. In the spinal cord of trained, transected rats, the ventral horn showed significant changes, while the change in dorsal horn was insignificant. Von Frey's test indicated analgesia in all exercise-trained rats. The sciatic nerve functional index indicated recovery in the trained group. Thus, both the aerobic treadmill exercise training and the nervous lesion appear to contribute to changes in serotonin immunoreactivity.

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

“…While sedentary inflamed rats experienced ongoing deficits in weight bearing over the three-week period, inflamed rats engaging in voluntary running exhibited a steady improvement in weight bearing capacity of the ipsilateral paw, achieving basal levels by three weeks post-CFA. In studies using forced exercise paradigms, while not all groups describe complete exercise-induced reversal of hypersensitivity to von Frey stimulation, most produce progressive improvements over spans of a few days to more than five weeks [9; 11; 18–24; 35; 54; 63; 69; 82; 93; 102; 103; 112; 132]. Strikingly, development of the CFA-induced thermal hypersensitivity observed in the sedentary inflamed group was prevented by only one week of voluntary running.…”

“…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].…”

Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

“…The serotonergic system modulates both nociceptive and motor spinal cord circuits, 28,31,32,39,45,52,57 and motor activity increases the release of serotonin within spinal and supraspinal areas parallel to reduction of mechanical hyperalgesia. 29,33 Moreover, physical exercise decreases NKCC1 levels and restores KCC2 along with recovery of inhibitory reflex responses in spinal cord injured rats. 14 We suggest that the increased activity induced by our treadmill protocol may act similarly by upregulating serotonin activity and may stimulate PKC to restore KCC2-dependent disinhibition to pain after peripheral nerve injury.…”

Regular physical activity prevents development of chronic pain and activation of central neurons

“…Most of these studies started exercise at the time of injury or after development of hyperalgesia and show a reversal of the hyperalgesia with as little as a single treatment (3,33,51,58). However, Kuphal and colleagues show that 7 days of exercise prior to induction of inflammatory pain with formalin or 2 wk of exercise prior to induction of neuropathic pain attenuated the development of pain behaviors.…”