Control of chronic pain by the ubiquitin proteasome system in the spinal cord.

Chronic pain is maintained in part by long-lasting neuroplastic changes in synapses and several proteins critical for synaptic plasticity are degraded by the ubiquitin-proteasome system (UPS). Here, we show that proteasome inhibitors administered intrathecally or subcutaneously prevented the development and reversed nerve injury-induced pain behavior. They also blocked pathological pain induced by sustained administration of morphine or spinal injection of dynorphin A, an endogenous mediator of chronic pain.

Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis.

Background & Aims: Pain is a main complaint of patients with pancreatitis. We hypothesized that such pain is mediated through ascending pathways via the nucleus gracilis (NG) and is dependent on descending facilitatory influences from the rostral ventromedial medulla (RVM).

Methods: A rat model of persistent experimental pancreatitis was used.