Actions of cholinergic agonists and antagonists on sensory nerve endings in rat skin, in vitro.

1. Cholinergic effects on primary sensory afferents were investigated in a superfused skin-saphenous nerve preparation of the rat that allows the application of chemicals topically to the corium side of identified receptive fields. 2. The acetylcholine analogue carbachol (carbamoylcholine) selectively excited cutaneous C-fibers of nociceptive character; in proportion, almost half of the mechanoheat sensitive ("polymodal," C-MH, n = 27), and a third of the mechanocold sensitive (C-MC, n = 10), and high-threshold mechanosensitive (C-HTM, n = 6) C-fibers were activated. 3. None of slowly and rapidly adapting A beta fibers, low and high threshold mechanoreceptive A delta fibers (n = 19) gave a response to high concentrations (< or = 10(-4) M) of carbachol. 4. The carbachol threshold concentrations of C-nociceptors ranged between 10(-7) and 10(-4) M; 10(-6) M was most frequently encountered. 5. The carbachol-induced discharges showed a dose-response relationship without obvious "ceiling" from 10(-6) to 10(-4) M. Tachyphylaxis was not prominent; the fibers mostly developed ongoing activity after exposure to carbachol. 6. Repeated carbachol treatment of C-MH units left with a marked and sustained desensitization to mechanical (von Frey) stimulation, while the heat responsiveness remained unchanged. 7. In a group of carbachol-sensitive C-nociceptors (n = 4), two units could also be excited with muscarine (10(-6) M), one with nicotine (10(-6) M), and one unit with both substances.(ABSTRACT TRUNCATED AT 250 WORDS)