Change of dorsal horn neurochemistry in a mouse model of neuropathic cancer pain

Abstract 

We investigated some neurochemical changes that take place in the spinal cord dorsal horn in a mouse model of neuropathic cancer pain. The model was produced by inoculation of Meth-A sarcoma cells to the vicinity of the sciatic nerve, which resulted in growth of a tumor mass embedding the nerve. Hind paw-lifting, a behavioral sign of spontaneous pain, was at maximum on Day 18, but decreased thereafter. The decrease was likely caused by progression of motor paralysis. On Day 18, thermal and mechanical pain thresholds of the affected paw were significantly increased. Histologically, the sciatic nerve presented damages to both unmyelinated and myelinated fibers on Day 18, which were more pronounced on Day 25. In the spinal cord, c-Fos-positive cells were significantly increased in the superficial and deep layers on Day 18. The number of c-Fos-positive cells in the superficial layer correlated with the duration of paw-lifting. The increase in c-Fos-positive cells was still present on Day 25 despite decreased paw-lifting. Substance P and calcitonin gene-related peptide were up-regulated on Day 18 but down-regulated on Day 25. A marked up-regulation of dynorphin A (DynA) was present on Day 18 and persisted through Day 25. Our model caused progressive damage to the sciatic nerve and presented spontaneous pain-behavior while the paw became hyposensitive to mechanical and thermal stimuli. Since the up-regulation of DynA in the dorsal horn persisted and paralleled the increase in c-Fos-positive cells, the release of DynA may be associated with spontaneous pain in our model.

Keywords: c-Fos, Calcitonin gene-related peptide, Neuropathic pain, Spontaneous pain, Dorsal horn, Dynorphin A