Changes of substance P-like immunoreactivity in the dorsal horn are associated with the 'phasic' behavioral response to a formalin stimulus.

Substance P (SP) has been proposed as a nociceptive transmitter/modulator in the dorsal horn of the spinal cord. Formalin used as a nociceptive stimulus has been shown to increase, in a biphasic manner, the amount of immunoreactive SP in the dorsal horn. The time course of the changes in substance P-like immunoreactivity (SPLI) caused by formalin is similar to both the electrical activity of dorsal horn neurons and licking behaviors. The administration of morphine reduces stereotypic behaviors caused by a formalin injection but actually increases the amount of SPLI in the dorsal horn. Therefore, the extent to which SP in the dorsal horn is involved with nociception as a result of formalin remains uncertain. To test the involvement of SP with chemogenic nociception, we utilized lidocaine to block afferent activity prior to an injection of formalin and studied the time course of behaviors and SPLI changes in the dorsal horn. Our results showed that formalin produced two distinct phases of nociceptive behaviors as measured by stereotypic licking of the injected paw: an acute 'phasic' response followed by a longer-lasting 'subacute' or 'tonic' response. Lidocaine reduced both phases of stereotypic behaviors, but only reduced the first increase of SPLI in the dorsal horn. These results suggested a direct involvement of SPLI in the dorsal horn with only 'phasic' behavioral responses to a formalin stimulus.