Death in pain: peripheral nerve injury and spinal neurodegenerative mechanisms

A complex network operates in the spinal dorsal horn to integrate peripheral nociceptive inputs with local and descending control mechanisms, and to cross-talk with higher brain areas. Injury to peripheral sensory nerves can trigger a cascade of events within this relay which, in some cases, may turn into abnormal responses outlasting the initial detrimental stimulus and leading to chronic pain. In the spinal dorsal horn, evidence has been provided both in support and against the occurrence of neuronal loss following peripheral nerve injury, leaving this issue still unresolved. Only new conceptual and technical approaches will determine the relevance of spinal neurodegenerative mechanisms to chronic pain states and allow translation into novel therapeutic targets.