Responses of Rat Spinal Dorsal Horn Neurons to Intracutaneous Microinjection of Histamine, Capsaicin, and Other Irritants

Abstract

Carstens, E. Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. J. Neurophysiol. 77: 2499–2514, 1997. To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-type lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses were recorded to mechanical and noxious thermal stimuli, as well as to microinjection (1 μl) of histamine (0.01–10% = 9 × 10−1–9 × 10−4 M), capsaicin (0.1% = 3.3 × 10−3 M), or other algesic chemicals into skin within the receptive field via intracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (ic) microinjection of histamine with a brief phasic discharge followed by an afterdischarge of variable (s to min) duration. 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 tachyphylaxis when histamine microinjections were repeated at 5- or 10-min intervals. Unit responses significantly increased in a dose-related manner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after ic microinjection of the H1 antagonist cetirizine, unit responses to ic histamine delivered at the same skin site were significantly attenuated. Unit responses to histamine, as well as to noxious thermal stimulation, were significantly reduced after systemic administration of morphine (3.5 mg/kg ip) in a naloxone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to ic histamine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were markedly 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 capsaicin, subsequent responses to histamine and capsaicin microinjections were significantly reduced. Units also responded to ic ethanol (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to repeated ic ethanol at 80% but not at 8%. The mean response to 80% ethanol was significantly smaller than to 0.1% capsaicin. All units tested also responded to topical application of mustard oil (50%) and ic serotonin (30 μg). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.