RESPONSES OF RAT SPINAL DORSAL HORN NEURONS TO INTRACUTANEOUS MICROINJECTION OF HISTAMINE, CAPSAICIN, AND OTHER IRRITANTS

To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-typ e lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetiz ed rats. Neuronal responses were recorded to mechanical and noxious th ermal stimuli, as well as to microinjection (1 mu 1) of histamine (0.0 1 - 10% = 9 x 10(-1)-9 x 10(-4) M), capsaicin (0.1% = 3.3 x 10(-3) M), or other algesic chemicals into skin within the receptive field via i ntracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (ic) microinjection of histamine with a brief phasi c discharge followed by an afterdischarge of variable (s to min) durat ion. Ten minutes after ic microinjection of histamine (but not NaCl), there was a significant increase in the mean area of the low-threshold (but not high-threshold) portion of unit mechanical receptive fields. However, responses to graded pressure stimuli were not significantly affected after histamine. Responses did not exhibit significant tachyp hylaxis when histamine microinjections were repeated at 5- or 10-min i ntervals. Unit responses significantly increased in a dose-related man ner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after ic microinjection of the H-1 an tagonist cetirizine, unit responses to ic histamine delivered at the s ame skin site were significantly attenuated. Unit responses to histami ne, as well as to noxious thermal stimulation, were significantly redu ced after systemic administration of morphine (3.5 mg/kg ip) in a nalo xone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to ic histam ine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were marked ly suppressed by electrical stimulation in the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested also responded to ic microinjection of capsaicin. After the initial microinjection of ca psaicin, subsequent responses to histamine and capsaicin microinjectio ns were significantly reduced. Units also responded to ic ethanol (cap saicin vehicle) in a dose related manner, and showed tachyphylaxis to repeated ic ethanol at 80% but not at 8%. The mean response to 80% eth anol was significantly smaller than to 0.1% capsaicin. All units teste d also responded to topical application of mustard oil (50%) and ic se rotonin (30 mu g). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.