Effects of iontophoretically released peptides on primate spinothalamic tract cells

Abstract

The peptides substance P (SP), methionine-enkephalin (M-ENK), leucine-enkephalin (L-ENK), and cholecystokinin (CCK) were released iontophoretically near spinothalamic tract (STT) cells in anesthetized monkeys and STT-like cells in decorticate, spinalized monkeys. Peptide effects were observed on background discharges, firing induced by release of glutamate, and activity evoked by pinching the skin. SP could have any of several actions on STT cells, including excitation, inhibition, or biphasic effects. Multiple effects often resulted while recording from an individual cell when the dose or the electrode position was changed. M-ENK and L-ENK generally inhibited STT cells, and in some cases it was possible to demonstrate a reversal of the inhibition by naloxone. CCK also caused an inhibition that was additive with that produced by L-ENK. The multiple actions of SP on STT cells suggests the possibility that there may be more than one type of SP receptor on STT cells, although alternative explanations should be considered. Inhibition of STT cells by M- and L-ENK is consistent with the known analgesic action of opiates through spinal cord mechanisms. CCK has an action on STT cells similar to that of the enkephalins.

Actions of opioids on primate spinothalamic tract neurons

“…Agonists of all of the opiate receptor subtypes tested (p, K, 6, c) had effects on these cells. The predominant action was inhibitory, confirming previous observations of opiate effects on dorsal horn nociceptive neurons (see reviews by Duggan and North, 1984;Zieglg%nsberger, 1984) and our own study of the action of enkephalin on STT cells (Willcockson et al, 1984b). …”

“…The only opioid substances tested were methionine and leucine enkephalin (Willcockson et al, 1984b), which produced a naloxone-reversible inhibition of STT cells. For the present investigation, we wished to examine the actions of other opioid substances.…”

Endogenous Analgesia, Dependence, and Latent Pain Sensitization

“…glutamate) release from the central terminals of primary afferent neurons (Jessell and Iversen, 1977, Duggan and North, 1983, Yaksh et al, 1988, Chang et al, 1989, Hori et al, 1992, Suarez-Roca and Maixner, 1992, Glaum et al, 1994, Terman et al, 2001), ultimately leading to inhibition of spinal excitatory pain transduction (Yoshimura and North, 1983). MORs are also an important postsynaptic target, as they are found in a population of mostly excitatory neurons in laminae I and II, where they inhibit the firing of action potentials, presumably leading to inhibition of nociceptive transmission to the brain (Willcockson et al, 1984, Jeftinija, 1988, Schneider et al, 1998, Kohno et al, 1999, Aicher et al, 2000). …”

Primary Afferent NMDA Receptors Increase Dorsal Horn Excitation and Mediate Opiate Tolerance in Neonatal Rats

“…Increased EPSC frequencies in morphine-tolerant slices are attributable to NMDA receptors A number of excitatory neurotransmitters in addition to glutamate have been reported to have activity in the spinal dorsal horn [including ATP (Ding et al, 2000), SP (Willcockson et al, 1984), and serotonin (Li and Zhuo, 1998)]. However, in our previous studies in opiate-naive slices ) CNQX, a glutamate antagonist at kainate/AMPA-type receptors, virtually eliminated all sEPSCs and eEPSCs in lamina I recordings, pointing to glutamate as the primary excitatory transmitter in this region.…”