THE EFFECT OF VOLUNATARY EXERCISE ON NEUROPATHIC PAIN

Abstract

Neuropathic pain results from damage to peripheral sensory axons, which can occur due to physical trauma (via nerve trauma) or metabolic diseases (via diabetes). Neuropathic pain can be a debilitating disease that often responds poorly from pharmacological interventions. The ability of exercise to reduce behavioral sensitivity associated with neuropathic pain in rodents has been reported; however, the exercise-induced mechanisms were not researched in this study. Increases in neurotrophic factors (e.g. glial cell line-derived neurotrophic factor [GDNF]) have been proposed as a possible mechanism for reducing neuropathic pain. Therefore, the purpose of this study is to determine whether voluntary exercise can attenuate or delayed mechanical sensitivity associated with neuropathic pain and assess GDNF levels as a possible mechanism. Two neuropathic pain models (SNI and streptozotocin [STZ]-induced diabetes [type 1 model]) were assessed. Following surgery and/or injections, animals in the exercised groups were housed in standard cages with voluntary running wheels while the sedentary group was housed without wheels. To quantify neuropathic pain mechanical allodynia and hyperalgesia were assessed. GDNF protein levels and mRNA expression were examined in the lumbar region of the spinal cord, dorsal root ganglion (DRG), sciatic nerve, and skeletal muscle. Our results showed that both models produced mechanical hypersensitivity. However, voluntary exercise significantly reduced mechanical hypersensitivity within 2 to 3 weeks. Within the spinal cord, the SNI surgery increased GDNF protein levels, whereas diabetes significantly decreased GDNF levels. Voluntary exercise had no effect on GDNF levels after nerve injury; however, among diabetic animals voluntary exercise significantly increased GDNF protein levels in the spinal cord and sciatic nerve, mRNA expression in skeletal muscle, along with axonal transport in the sciatic nerve. Intrathecal injections of recombinant GDNF ameliorated mechanical sensitivity associated with diabetic neuropathy, therefore implicating the potential therapeutic actions of GDNF. In summary, voluntary exercise caused favorable changes in behavioral sensitivity in both nerve-injured and diabetic rodents. In diabetic rodents this reduction in mechanical sensitivity may be due to an increase in GDNF and axonal transport, whereas the exercise-induced mechanism after nerve injury remains unknown. This investigation supports the use of exercise to complement current treatment strategies aimed at decreasing neuropathic pain associated with peripheral nerve injury and diabetes.