Adjuvant-induced inflammation of rat paw is associated with altered calcitonin gene-related peptide immunoreactivity within cell bodies and peripheral endings of primary afferent neurons.

Local inflammation is associated with profound changes in the biochemistry and physiology of primary afferent nerve fibers and the central neurons responding to their signals. In some tissues, the neural changes accompanying inflammation include sprouting and cytochemical changes that are delayed several days after the initial injury. In the present study, we have analyzed the effect of complete Freund's adjuvant (CFA)-induced inflammation in the rat paw on calcitonin gene-related peptide (CGRP) immunoreactivity (IR) in dorsal root ganglia and within tissue of the inflamed paw. We quantified the CGRP-IR within the L1, L4, and L6 ganglia, and in ankle, midpaw, joint and toe tissues. Analysis of the processed tissue revealed a significant increase in the percentage of CGRP-positive cells within L4 dorsal root ganglia ipsilateral to an inflamed hindpaw six days after administration of CFA. There was a parallel increase in the number and staining density of detectable CGRP-immunoreactive fibers in periarticular and perivascular tissues of the inflamed digits and inflamed ankle. The other tissues of the paw, including epidermis and the regions surrounding the abcesses, did not have detectable changes in CGRP-immunoreactive fibers, despite tissue swelling and dystrophic changes in the foot that included loss of mast cell staining. These data demonstrate that local inflammation of the rat paw has delayed influences on the peripheral nervous system, in addition to a number of previously characterized acute effects. The alterations of CGRP-IR were focused around specific tissue types, such as joints and subdermal blood vessels, and absent from others, such as epidermis or in the areas surrounding abscesses. This suggests production of local factors within reactive tissues that selectively interact with nerve fibers to induce changes in CGRP-IR within the fibers.