Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin

Research using animal models of neuropathic pain has revealed sympathetic sprouting onto dorsal root ganglion cells. More recently, sensory fibre sprouting onto dorsal root ganglion cells has also been observed. Previous work in our laboratory demonstrated persistent sympathetic fibre sprouting in the skin of the rat lower lip following sensory denervation of this region. Therefore, we applied immunocytochemistry to determine the effects of sympathectomies on the terminal fields of sensory fibres. The superior cervical ganglia were removed bilaterally and the effects on the innervation of the skin of the rat lower lip were observed 1, 2, 3, 4, 6 and 8 weeks post-surgery. Substance P and dopamine-β-hydroxylase immunoreactivities were used to identify a subset of sensory and sympathetic fibres, respectively. We also assessed neurokinin-1 receptor immunoreactivity. Quantitative data was obtained with the aid of an image analysis system. In controls, the epidermis and upper dermis were innervated by substance P-immunoreactive fibres only and upper dermal blood vessels possessed the highest density of neurokinin-1 receptor immunoreactivity. Blood vessels in the lower dermis were innervated by both substance P- and dopamine-β-hydroxylase-immunoreactive fibres. Following sympathectomies, substance P-immunoreactive fibres in the epidermis and upper dermis were more intensely labelled only 1 and 2 weeks post-surgery when compared to sham controls. The length of substance P-immunoreactive fibres in this region was also increased only on the second week. Neurokinin-1 receptor immunoreactivity in the upper dermis was slightly decreased 1 and 2 weeks post-surgery. In the lower dermis, substance P-immunoreactive fibres associated with blood vessels were more intensely labelled only 1 and 2 weeks post-surgery, and at all post-surgical time points studied, blood vessels in this region were devoid of dopamine-β-hydroxylase-immunoreactive fibres. The length of substance P-immunoreactive fibres was increased from the first to the third week post-surgery in the lower dermis. These results indicate that sympathectomies lead to transient changes in substance P-immunoreactive fibre innervation and neurokinin-1 receptor expression in rat lower lip skin. The effects are most prominent in the lower dermis probably due to a greater local concentration of nerve growth factor in this region. The plasticity of the interactions between sensory and sympathetic fibres may prove important in the regulation of skin microcirculation and in the generation of painful sensations under normal conditions or following peripheral nerve injuries.