C‐fos expression at the spinal dorsal horn of streptozotocin‐induced diabetic rats

Abstract

Pain during diabetic neuropathy is associated with peripheral nerve damage but recent evidences suggest the occurrence of central effects. We used the activation of the c-fos protooncogene to study the activity of spinal dorsal horn neurons in streptozotocin (STZ)-induced diabetic rats in the absence of stimulation or in response to innocuous or noxious stimuli. Four weeks after saline or STZ (50 mg/kg) injection, rats were anaesthetized and either not further manipulated or submitted to innocuous (gentle touch), noxious mechanical (pinching) or noxious thermal (radiant heat) stimulation of the hindlimb skin. In each experimental situation, the numbers of Fos-immunoreactive (Fos-IR) neurons occurring in the superficial (laminae I-II) or deep (laminae III-V) dorsal horn were compared. In the absence of stimulation, STZ-injected rats presented significantly higher numbers of Fos-IR neurons than controls, both in the superficial and deep dorsal horn (DDH). In comparison with the respective baseline levels, innocuous stimulation did not induce a significant increase in the numbers of Fos-IR neurons in controls or STZ-rats. Noxious mechanical and noxious thermal stimuli increased the numbers of Fos-IR neurons, both in control and STZ-rats, but in a more pronounced manner when diabetic rats were subjected to noxious mechanical stimulation. The present study demonstrates that the responses of spinal cord neurons are strongly affected during diabetes. The higher baseline neuronal activity probably underlies the spontaneous pain detected during diabetes since the spinal dorsal horn is the major relay station in the ascending transmission of nociceptive input to the brain.