INTRATHECAL ADENOSINE ANALOG ADMINISTRATION REDUCES SUBSTANCE-P IN CEREBROSPINAL-FLUID ALONG WITH BEHAVIORAL-EFFECTS THAT SUGGEST ANTINOCICEPTION IN RATS
Kf. Sjolund et al., INTRATHECAL ADENOSINE ANALOG ADMINISTRATION REDUCES SUBSTANCE-P IN CEREBROSPINAL-FLUID ALONG WITH BEHAVIORAL-EFFECTS THAT SUGGEST ANTINOCICEPTION IN RATS, Anesthesia and analgesia, 85(3), 1997, pp. 627-632
Adenosine and adenosine analogs induce analgesia in humans and presume
d antinociception in animal models when administered both systemically
and intrathecally. In the present investigation in rats, we studied t
he effects of intrathecally administered adenosine analogs, with or wi
thout systemic coadministration of an adenosine antagonist (theophylli
ne), on substance P (SP) and calcitonin gene-related peptide (CGRP) co
ncentrations in cerebrospinal fluid (CSF). In parallel, nociceptive re
flex testing (tail immersion latency) and motor function were evaluate
d. The potent unselective adenosine receptor agonist N-ethylcarboxamid
e-adenosine (NECA) and the relatively adenosine A(1) receptor selectiv
e agonist R-phenylisopropyl-adenosine (R-PIA) both reduced SP-like imm
unoreactivity (-LI) by 50%, whereas CGRP-LI remained unchanged. There
was a dose-dependent increase in tail immersion latency. This effect w
as present without motor impairment when R-PIA was administered in dos
es up to 5 nmol. R-PIA (10-100 nmol), as well as 1-100 nmol of the uns
elective agonist NECA, produced dose-dependent motor impairment. The r
eduction of SP-LI as well as the behavioral effects were reversed by t
heophylline. We conclude that SP reduction in CSF, which possibly refl
ects reduced SF turnover after adenosine receptor stimulation, provide
s an additional possible mechanism of action for the analgesic effects
of adenosine. Implications: We studied the interactions between the k
nown pain mediator substance P and substances with effects similar to
the endogenous pain modulator adenosine in rats. The results suggest t
hat the pain-reducing effect of adenosine is, at least partly, due to
a seduction of substance P in cerebrospinal fluid.