To the Editor:

My colleagues and I thank Dr. Straub for his letter regarding our article. As he noted, there appears to be significant heterogeneity in the literature concerning the changes in sympathetic innervation that occur in different inflammatory pain states (1–7). We agree that changes in the sensory and sympathetic innervation in an inflamed tissue depend on a variety of factors, including the type of model, the tissue being investigated, postmortem examination, and methods of tissue collection and storage.

As stated in the Discussion of our report, robust sprouting of tyrosine hydroxylase–positive postganglionic sympathetic nerve fibers was observed in the inflamed synovium of the painful arthritic joints in mice, and anti–nerve growth factor therapy blocked this sprouting. We attempted to address these differences in our results versus those of others by stating that “… several reports have suggested that sympathectomy attenuates disease progression and/or pain in arthritis (18–20) [8–10 herein], although sympathectomy-induced enhancement of disease and/or pain in arthritis has also been reported (21–23) [11–13 herein]. Whether these differences are due to the different species, models of arthritis, or methods of performing sympathectomy that were used in these studies remains unclear.”

Given the limitations in terms of both word count and number of references allowed in this type of communication, the article was not meant to be a systematic review of the heterogeneous literature concerning the changes that sympathetic nerve fibers undergo in different inflammatory pain states. Rather, the study was intended to demonstrate that significant sprouting of sensory and sympathetic nerve fibers can occur in the painful inflammatory joint. Thus, while the role of sensory and sympathetic nerve plasticity in inflammatory disease–related pain states is not completely understood, the present findings suggest that significant neuroplasticity can occur, and we agree that further studies are needed to understand the physiologic significance of the neuroplasticity of sensory and sympathetic nerve fibers (whether it be an increase or decrease) that frequently occurs in inflammatory states.

Patrick W. Mantyh PhD, JD*, * University of Arizona, Tucson, AZ.