A pan-caspase inhibitor reduces myocyte apoptosis and neuropathic pain in rats with chronic constriction injury of the sciatic nerve.

Background: Chronic constriction injury is a widely used model for neuropathic pain in rats. It presents with symptoms resembling human neuropathic pain, such as spontaneous pain, hyperalgesia, and allodynia. Recently, myocyte apoptosis was found in neuropathic rats as a possible promoter of pain and motor dysfunction.

Exaggeration of tissue trauma induces signs and symptoms of acute CRPS I, however displays distinct differences to experimental CRPS II.

As CRPS I frequently develops after tissue trauma, we proposed that an exaggerated inflammatory response to tissue trauma may underlie CRPS I. Therefore, we studied the vascular inflammatory, nociceptive and apoptotic sequelae of (i) soft tissue trauma and (ii) exaggerated soft tissue trauma in comparison to those of (iii) sciatic nerve chronic constriction injury, modeling CRPS II. Standardized soft tissue trauma (TR) was induced by means of a controlled impact injury technique in the hind limb of pentobarbital-anesthetized rats.

Supernatant of traumatized muscle induces inflammation and pain, but not microcirculatory perfusion failure and apoptotic cell death.

Soft tissue trauma induces an inflammatory response locally and in remote organs. Although remote organ failure is attributed to the systemic action of locally released mediators, it is so far unclear to what extent a direct cell injury and the consequences of ischemia or a secondary injury due to locally released mediators contribute to the manifestation of tissue damage at the primary site of trauma. Soft tissue trauma was induced by means of a controlled impact injury technique in the hind limb of pentobarbital-anesthetized rats.