1. Intrathecal (i.t.)
injections of the (
tachykinin) NK1 receptor agonist,
substance P methyl ester (
SPME; 20 pmol), or the NK2 receptor agonist,
neurokinin A (NKA; 20 pmol), substantially decreased the cutaneous mechanical threshold and markedly enhanced the touch-evoked response of posterior biceps femoris-semitendinosus (PBF-ST) spinal flexor motoneurones in decerebrate-spinal rats. This cutaneous mechanical reflex
allodynia was prevented by pretreatment with the NK1 antagonist
RP 67580 (2.28 nmol, i.t.) and the NK2 antagonist
MEN 10376 (0.7 nmol, i.t.), respectively. 2. Electrical stimulation of the sural nerve at C fibre strength or cutaneous application of the
irritant, mustard oil, produced prolonged cutaneous
mechanical allodynia in PBF-ST motoneurones (15 min and > 1 h, respectively). Pretreatment with
RP 67580 but not
MEN 10376 prevented this, but when
RP 67580 was administered 25 min after the application of mustard oil, the established
hypersensitivity of the flexor motor reflex was not reversed. The enantiomer of
RP 67580,
RP 68651 was without effect. 3. Injection of
bradykinin (60 microM, 80 microliters) into the gastrocnemius muscle increased the cutaneous mechanical
hypersensitivity of PBF-ST flexor motoneurones for 40-50 min.
MEN 10376, but not
RP 67580, prevented this, but only when administered prior to the
bradykinin injection. 4. These results suggest that the induction, but not the maintenance, of cutaneous
mechanical allodynia in flexor motoneurones is NK receptor dependent, with cutaneous C fibre conditioning inputs acting via NK1 and muscle C fibre conditioning inputs via NK2 receptor subtypes.