Dana M Lambert, Ujendra Kumar and Hafeli O
Chronic widespread musculoskeletal pain is a major cause of disability. Pro-inflammatory glial cell activity, also known as gliosis, has been associated with the development and maintenance of hyperalgesia within several forms of chronic pain, yet its role in the pathophysiology of chronic widespread musculoskeletal pain has not been clearly established. The aim of this study was to quantitatively compare the expression of glial cells in the acidic saline (AS) model of chronic widespread musculoskeletal pain with controls and determine whether a relationship exists between glial cell expression and pain response. Activation markers of astrocytes (GFAP) and microglia (Iba-1), detected via immunohistochemistry, were quantitatively analyzed in the lumbar spinal cord and thalamus ventrobasal complex. Hyperalgesia was determined using electronic algesiometer measurement of cutaneous mechanical withdrawal threshold. Five out of twenty-one (24%) AS animals developed bilateral hyperalgesia. The expression of Iba-1 and GFAP in the L5 and L6 spinal cord was found to be significantly increased in AS animals relative to controls, regardless of behavioural pain response (p<0.05). When sub-grouped according to pain response, only hyperalgesia responders showed increased lumbar Iba-1 expression (p<0.05 versus control). In contrast, both hyperalgesia responders and non-responders had increased lumbar GFAP expression (p<0.05 versus control). This study provides evidence of spinal cord gliosis in an animal model of chronic widespread musculoskeletal pain and suggests a positive correlation between lumbar microglia expression and hyperalgesia. This novel finding establishes a possible pathophysiological link between reactive gliosis and hyperalgesia in chronic widespread musculoskeletal pain disorders.