Parallels between lumbosacral radiculopathy and complex regional pain syndrome: α1-adrenoceptor upregulation, reduced dermal nerve fibre density and hemi-sensory disturbances in post-surgical sciatica.

Residual lower-limb pain after low back surgery (postsurgical sciatica) and complex regional pain syndrome (CRPS) involving a lower limb are separate conditions but may share some mechanisms (eg, tissue inflammation, neuroimmune disturbances, and central neuroplasticity). As adrenergically evoked pain contributes, in part, to CRPS, whether an adrenergic mechanism also contributes to postsurgical sciatica was investigated in this study. Immunohistochemistry was used to identify alpha(1)-adrenoceptors (alpha(1)-AR) on nerve fibres and other targets in the affected and contralateral skin of 25 patients with postsurgical sciatica, and alpha(1)-AR expression was investigated in relation to pain and pinprick hyperalgesia after intradermal injection of the alpha(1)-AR agonist phenylephrine. In addition, quantitative sensory testing was performed on all 4 limbs and on each side of the forehead. alpha(1)-AR expression was greater in keratinocytes (but not blood vessels or nerve fibres) in the symptomatic than contralateral leg, and dermal nerve fibre density was reduced in both legs. However, distal adrenergic involvement in pain in postsurgical sciatica seems unlikely, as neither heightened alpha(1)-AR expression in keratinocytes nor reduced dermal nerve fibre density were associated with pain or hyperalgesia to intradermal phenylephrine injection. Sensitivity to pressure-pain, pinprick, and cold-pain was greater in the ipsilateral than contralateral forehead of the entire cohort, but sensory disturbances were most pronounced in patients with additional CRPS-like features. Together, these findings suggest that bilateral distal neuropathy and central neuroplastic changes are involved not only in the pathophysiology of CRPS but also in postsurgical sciatica. This may have treatment implications for patients with postsurgical sciatica.