Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy B.D.X. Lascelles a,b, *, P.J. Cripps a , A. Jones a , A.E. Waterman a a Department of Clinical Veterinary Science, Division of Companion Animal Studies, Langford House, Langford, Bristol, BS18 7DU, UK b Department of Clinical Veterinary Science, University of Cambridge, Queen’s Veterinary School Hospital, Madingley Road, Cambridge, CB3 OES, UK Received 23 April 1997; revised version received 5 August 1997; accepted 27 August 1997 Abstract The effect of timing of analgesic drug administration on the severity of post-operative pain was investigated in dogs undergoing ovariohysterectomy using both subjective visual assessment scoring systems (VAS) and objective mechanical nociceptive threshold measurements using a novel handheld anti-nociceptiometric device. Forty dogs undergoing routine elective ovariohysterectomy were included in a randomised and double-blind study and assigned to one of three groups: (i) pre-operative analgesics; (ii) post-operative analgesics; (iii) no analgesics (saline injections). The analgesic used was pethidine (a short acting predominantly m-opioid agonist), at a dose of 5.0 mg/kg (intramuscular). The post-operative administration of pethidine resulted in significantly higher sedation scores and significantly lower pain scores in the early post-operative period, but the dogs given pethidine pre-operatively had significantly lower pain scores than both the other groups at 8, 12 and 20 h post-extubation (P  0.01, ANOVA). Mechanical thresholds measured at the distal tibia demonstrated the development of allodynia at 12 and 20 h post-extubation, and this was significantly prevented by the pre- (P  0.01 at 12 h, P  0.05 at 20 h, Kruskal-Wallis and post hoc Dunn’s), but not by the post-operative administration of pethidine. Mechanical nociceptive thresholds measured at the ventral midline (site of surgery) demonstrated post-operative hyperalgesia in all groups; this hyperalgesia was least in the pre-operative pethidine group. In summary, this study clearly shows pethidine to be an effective analgesic in dogs, albeit of short duration of action, when administered post-operatively, and, importantly, that it has a positive benefit in terms of post-operative outcome measures, when administered pre-operatively, possibly as a result of blocking or preventing the development of central sensitisation following surgical stimulation.  1997 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Pre-emptive; Analgesia; Dog; Opioid; Ovariohysterectomy; Central hypersensitivity 1. Introduction Laboratory studies investigating the pre-emptive effect of opioids have shown that pre-injury treatment with opioids (Woolf and Wall, 1986b; Dickenson and Sullivan, 1987) prevents or markedly decreases the development of central hypersensitivity, but that these treatments are far less effec- tive if administered after the injury is initiated (Woolf and Wall, 1986a; Dickenson and Sullivan, 1987; Chapman and Dickenson, 1993). Transposition of this argument to the clinical setting has produced equivocal results as regards whether or not the use of analgesics in a pre-emptive man- ner produces any clinical benefit in terms of post-operative pain. However, poor experimental design and confounding variables have confused the issue (Katz, 1995). In order to bridge the gap between basic scientific studies and the clin- ical situation, Lascelles et al. (1995a) investigated a clinical surgical procedure in a randomised double-blind placebo- controlled study in rats. They found a clear marked reduc- tion in post-operative hyperalgesia produced as a result of surgery, when pethidine was administered pre-operatively as opposed to post-operatively. The study reported here was designed to take these investigations to the next logical level, that is, to investigate the value of pre-emptive opioid Pain 73 (1997) 461–471 0304-3959/97/$17.00  1997 International Association for the Study of Pain. Published by Elsevier Science B.V. PII S0304-3959(97)00141-3 * Corresponding author.