Microglial reactions after subcutaneous formalin injection into the rat hind paw

Microglia in primary afferent projection territories are activated and prol iferate after peripheral nerve injury. However, it is not known whether sti mulation of peripheral nerves by noxious stimuli applied to their receptive fields activates microglial cells in the spinal cord. This study was desig ned to investigate the response of microglia in the lumbar spinal cord and in the brainstem to a tonic noxious stimulus. Thirty-two male Sprague-Dawle y rats received subcutaneous injections of 5% formalin (50 mu l) into the p lantar surface of the right hind paw, and 24 rats were injected with 50 mu l saline as a control. The lumbar spinal cord and brainstem were evaluated for immunoreactivity (IR) to complement receptor C3bi (monoclonal antibody OX-42) and major histocompatibility complex class LI (monoclonal antibody O X-6) on postinjection hours 0, 2, 4 and 8 and days 1, 3, 7, 14 and 28. A qu alitative and quantitative increase of OX-42-IR microglial cells were obser ved in the medial portion of the dorsal horn and in the gracile nucleus of the brainstem on the side ipsilateral to the formalin injection, starting o n days 1-3 and peaking on day 7 postinjection. OX-6-positive cells were sca ttered both in gray and white matter, but no difference was detected betwee n the two sides of the spinal cord or between formalin-injected and control animals. This is the first study that reports that subcutaneous injection of formalin into the rat's hind paw induces microglial activation in the sp inal cord as well as in the brainstem. Although we have not determined whet her these responses result from nociceptor activity, peripheral inflammatio n, or degeneration of primary afferents and/or central neurons, this method provides a simple, effective and stable animal model that will permit the future study of the mechanisms that contribute to microglial activation and its pathophysiological consequences. (C) 1999 Elsevier Science B.V. All ri ghts reserved.