Nociceptive signals may be enhanced or inhibited (gated) in the
dorsal horn of spinal cord (and also in the thalamus, although the higher up
the pathway one goes, the less is known). Placebo is an important effect in
people (much more important than the pharmacodynamic effect for some drugs such
as codeine); this must be mediated by the cortex. Placebo effects probably occur
in animals, but nocebo may be more important. Animals tend to recognise vets
who have done nasty things to them and seem to expect more of the same. This
is likely to affect the action of analgesic drugs adversely. Many analgesics
mimic or inhibit the action of the endogenous transmitters involved in gating
at the spinal level.
| transmission | transmitter | receptor | analgesic |
| normal | glutamate | AMPA | local |
| enhanced | glutamate | NMDA | ketamine, amitriptyline |
| substance P | NK1 | (capsazepine) | |
| neurokinin A | NK2 | (experimental drugs) | |
| nociceptin | ORL1 | (nociceptin antagonists) | |
| reduced | encephalins | μ and κ opioid | opioids (acupuncture?) |
| noradrenaline | α2 | α2 agonists | |
| 5HT | 5HT3? | antidepressants? | |
| GABA | GABAA | anaesthetics |
