Exploring the Metabolic, Activity, and Musculoskeletal Changes in Neuropathic Pain.

Abstract

Neuropathic pain is a major health concern. The study of neuropathic pain has predominantly focused on anatomical and physiological changes involved in the processing of sensory information. Knowledge gained from this body of research has led to advances in treatment. However, little attention has focused on metabolic alterations, physical activity responses, and musculoskeletal changes associated with neuropathic pain. In addition, the ability of drugs to prevent these changes remains explored. Our initial exploratory study used an established preclinical model of neuropathic pain, the chronic constriction injury (CCI), to investigate the relationships between neuropathic pain and muscle function by describing the metabolic, activity, and musculoskeletal changes following nerve injury. CCI rats had greater sensitivity to a thermal stimulus, a sign of neuropathic pain, compared to control rats that received sham surgery (SHAM). Increases in fasting free fatty acids were seen in both CCI and SHAM rats, but were likely due to natural weight gain and not a consequence of neuropathic pain. Fasting glucose significantly decreased in CCI rats. Conversely, insulin increased following nerve injury, but only trended significant. No changes in insulin resistance were observed in CCI rats. Spontaneous activity decreased after nerve injury, but not significantly (p = 0.06). Significant muscle atrophy of the soleus and extensor digitorum longus muscles of the injured hindlimb was present in CCI rats two weeks after surgery. Duloxetine, an antidepressant approved for the treatment of neuropathic pain, was used in a subsequent study to determine if muscle atrophy and activity changes could be prevented by improving altered nociceptive processing in CCI rats. Despite daily duloxetine administration for two weeks, CCI rats developed muscle atrophy and mechanical allodynia, a sign of neuropathic pain. Changes in activity or thermal hyperalgesia were not present in our CCI rats, but methodological factors may have contributed to negative findings. Our results contribute to the expanding body of knowledge regarding neuropathic pain. Future research will investigate the underlying mechanisms involved in activity changes and muscle atrophy in CCI rats.