Activation of Neurons in Rat Trigeminal Subnucleus Caudalis by Different Irritant Chemicals Applied to Oral or Ocular Mucosa

Abstract

Carstens, E., Nicole Kuenzler, and H. O. Handwerker. Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa. J. Neurophysiol. 80: 465–492, 1998. To investigate the role of trigeminal subnucleus caudalis in neural mechanisms of irritation, we recorded single-unit responses to application of a variety of irritant chemicals to the tongue or ocular mucosa in thiopental-anesthetized rats. Recordings were made from wide dynamic range (WDR) and nociceptive-specific units in superficial layers of the dorsomedial caudalis (0–3 mm caudal to obex) responsive to mechanical stimulation and noxious heating of the ipsilateral tongue (“tongue” units) and from WDR units in ventrolateral caudalis (0–2 caudal to obex) responsive to mechanical and noxious thermal stimulation of cornea-conjunctiva and frequently also surrounding skin (“cornea-conjunctival” units). The following chemicals were delivered topically (0.1 ml) onto the dorsal anterior tongue or instilled into the ipsilateral eye: capsaicin (0.001–1% = 3.3 × 10−2 to 3.3 × 10−5 M), ethanol (15–80%), histamine (0.01–10% = 9 × 10−1 to 9 × 10−4 M), mustard oil (allyl-isothiocyanate, 4–100% = 4 × 10−1 to 10 M), NaCl (0.5–5 M), nicotine (0.01–10% = 6 × 10−1 to 6 × 10−4 M), acidified phosphate buffer (pH 1–6), piperine (0.01–1% = 3.5 × 10−2 to 3.5 × 10−4 M), serotonin (5-HT; 0.3–3% = 1.4 × 10−1 to 1.4 × 10−2 M), and carbonated water. The dose-response relationship and possible tachyphylaxis were tested for each chemical. Of 32 tongue units, 31 responded to one or more, and frequently all, chemicals tested. The population responded to 75.3% of the various chemicals tested (≤10 per unit). The incidence of responses was independent of the order of chemicals tested, except for capsaicin, which reduced subsequent responses. Responses to histamine, nicotine, 5-HT, and ethanol had a more rapid onset and shorter duration compared with capsaicin, acid, and mustard oil. Responses to all chemicals increased in a dose-related manner. Successive responses to repeated application decreased significantly for nicotine, 5-HT, capsaicin, and piperine. Spontaneous firing increased significantly 5–10 min after initial application of capsaicin. Of 31 corneal-conjunctival units, 29 responded to one or more chemicals, and the population responded to 65% of all chemicals tested. Responses increased in a dose-related manner for all chemicals, and successive responses decreased significantly for histamine, nicotine, ethanol, acid, and capsaicin. Responses of tongue units to histamine and nicotine were reduced significantly by ceterizine (H1 antagonist) and mecamylamine, respectively. Mecamylamine also significantly reduced responses of corneal-conjunctival units to nicotine. Different classes of irritant chemicals contacting the oral or ocular mucosa can activate individual sensory neurons in caudalis, presumably via independent peripheral transduction mechanisms. Multireceptive units with input from the tongue or cornea-conjunctiva exhibited a similar spectrum of excitability to different irritant chemicals. Such neurons would not be capable of discriminating among different chemically evoked irritant sensations but could contribute to a common chemical sense.