[PDF][PDF] Capsaicin-induced depletion of substance P from primary sensory neurones

TM Jessell, LL Iversen, AC Cuello - Brain research, 1978 - academia.edu
TM Jessell, LL Iversen, AC Cuello
Brain research, 1978academia.edu
The peptide substance P is highly concentrated in terminals of small diameter primary
sensory neurones located within the substantia gelatinosa of the dorsal horn of the spinal
cord 2, 9. When applied iontophoretically substance P excites neurones in the dorsal horn
that respond to noxious peripheral stimuli 8,') e, and the peptide is released from the isolated
rat spinal cord in response to electrical stimulation of dorsal roots 22. These observations
strongly support the concept that substance P acts as a primary sensory transmitter 21, 24 …
The peptide substance P is highly concentrated in terminals of small diameter primary sensory neurones located within the substantia gelatinosa of the dorsal horn of the spinal cord 2, 9. When applied iontophoretically substance P excites neurones in the dorsal horn that respond to noxious peripheral stimuli 8,') e, and the peptide is released from the isolated rat spinal cord in response to electrical stimulation of dorsal roots 22. These observations strongly support the concept that substance P acts as a primary sensory transmitter 21, 24, possibly associated with the transmission of pain 8,'-'6. The pioneering studies of Jancso 11 and later, of Knyihar and Csillik17, 18 have shown that within the spinal cord the distribution of fluoride-resistant acid phosphatase activity is also highly restricted to the substantia gelatinosa and enzyme activity is possibly associated with primary afferent terminals involved in the processing of nociceptive stimuli. In support of this hypothesis is the finding that the administration of capsaicin, which is known to desensitize peripheral receptors responding to painful chemogenic stimuli, virtually abolishes the fluoride-resistant acid phosphatase activity of the substantia gelatinosa 13. Jancso xl has speculated that the densensitization to painful stimuli produced by capsaicin is explained by an inhibition of transmitter release from primary sensory neurones. However, the identity of the transmitter or transmitters affected by capsaicin is unknown. The striking similarity between the distribution of substance P and the fluoride-resistant acid phosphatase in spinal cord led us to investigate the possibility that capsaicin-induced desensitization may be mediated by an action on substance P-containing primary afferent terminals in the substantia gelatinosa.
Male Wistar rats weighing 150 g were treated daily for 5 days with increasing doses of capsaicin (Sigma Chemicals) given by subcutaneous injections. Capsaicin was dissolved in 0.1 ml of an emulsion of ethanol-Tween 80-water, as described previously 1: 3. The treated animals were injected from day 1 to day 5 with 50, 100, 200, 200 and 400 mg/kg of capsaicin. Control animals were injected with equal volumes of
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