A.E. Waterman

Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy.

&NA; 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 &mgr;‐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 Dunns), 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.

Central sensitization as a result of surgical pain: Investigation of the pre-emptive value of pethidine for ovariohysterectomy in the rat

&NA; The development of central hypersensitivity as a result of a routine surgical procedure, midline ovariohysterectomy, was investigated in rats using the paw pressure test (PPT) and tail‐flick latency (TFL) tests of spinal reflex activity. In addition, the modulating effect of pre‐emptive versus post‐operative administration of pethidine (a short‐acting pure &mgr;‐opioid agonist) on the development of central hypersensitivity was studied. Initial experiments indicated that pethidine (15 mg/kg, i.m.) gave sub‐maximal increases in thresholds for 60 min, and also that the administration of an anaesthetic did not unduly prolong the action of pethidine. Subsequently, 24 female Wistar rats were allocated to 1 of 4 treatment protocols: (1) anaesthesia without analgesics; (2) anaesthesia and surgery (midline ovariohysterectomy) without analgesics; (3) anaesthesia and surgery with pre‐operative administration of pethidine; (4) anaesthesia and surgery with post‐operative administration of pethidine. Thirty‐five minutes after the end of anaesthesia thermal and mechanical nociceptive thresholds were measured at stepwise increasing intervals for 480 min. Changes were expressed as percentage changes from baseline (PPT) or deviation from expected values (TFL). Area under the threshold versus time response curves (AUCs) were also calculated for the following time sectors: 30–90, 90–150, 150–270, 270–390 and 390–510 min post‐anaesthetic. Results of the TFL testing did not indicate the development of any significant hyperalgesia in any groups, but the results of the PPT did. In the time sectors 150–270 and 270–390 min post‐anaesthetic, the AUCs in rats subjected to anaesthesia and surgery with either post‐operative administration of pethidine or surgery with no analgesic drug administration, were significantly lower than the AUCs in rats given analgesics pre‐operatively or those subjected to general anaesthesia alone (P < 0.01, Mann‐Whitney). In summary, it appears that pethidine, in this protocol, prevented the development of surgically induced hyperalgesia when it was given pre‐emptively.

Techniques for comparison of thermal and mechanical nociceptive stimuli in the sheep

The assessment of analgesia in conscious unrestrained farm animals presents particular problems. In order to provide a reliable nociceptive stimulus, two devices have been constructed, one that provides a threshold reading for a ramped thermal stimulus of the pinna of the ear and another that measures a threshold reading for a pressure stimulus to the foreleg. Both devices allow the rapid termination of the stimulus once a reaction has occurred and allow repeated readings without causing tissue damage. Examples of the analgesic action of alpha 2-adrenoceptor agonists and opioids measured by using the two pieces of apparatus are shown.

The effect of chronic clinical pain on thermal and mechanical thresholds in sheep

&NA; Threshold responses were measured to a thermal skin test and a mechanical pressure test in two groups of conscious unrestrained sheep. The first group of sheep were healthy adult females and formed a control sample, the second group were also adult females, but were all suffering from a condition known as footrot. Footrot is a chronic infective lesion affecting usually one foot which appears to cause severe pain in its worst manifestation. These sheep were assessed for the severity of the lesion and degree of lameness and were divided into high and low severity subgroups. Footrot did not alter the threshold to the thermal test but the mechanical pressure threshold was significantly reduced in both footrot sub‐groups compared to controls. A local anaesthetic block of the affected foot restored values to close to the control level. After treatment of the affected foot, the mechanical threshold in the low severity sub‐group was returned to normal, but in the high severity sub‐group it was still significantly reduced compared to the control animals. However, when retested 3 months later these values had returned to the normal control levels.

Investigation of the antinociceptive activity of buprenorphine in sheep

1 Buprenorphine given intravenously (6 μg kg−1) was examined for its antinociceptive activity in unrestrained sheep using devices to measure thermal and mechanical thresholds 2 The plasma levels of buprenorphine following intravenous injection over the time period of the antinociceptive testing were measured using a radioimmunoassay. 3 Buprenorphine produced a clear antinociceptive effect lasting for up to three and a half hours when measured by the thermal threshold test, but no detectable antinociception in the mechanical test. 4 The plasma levels of buprenorphine indicated that the drug was rapidly distributed in a manner not dissimilar to that reported in man, although individual animals showed a wide variation in some parameters. 5 When plasma levels of the drug were high (< 700 pg ml−1) during the first sixty minutes, no antinociceptive activity in the thermal test could be detected, which may be due to the slow receptor kinetics shown by this drug.

Analgesic activity and respiratory effects of butorphanol in sheep

The analgesic drug butorphanol tartrate has proved useful clinically in horses and dogs but its analgesic profile had not yet been investigated in sheep. This study was initiated to determine the thermal and mechanical antinociceptive activity of butorphanol (at the dose rates 0.05, 0.1 and 0.2 mg kg-1) in sheep. The drug produced significant analgesia in the thermal test system, the duration of which was dose related but no significant elevation in mechanical pressure thresholds could be detected. In a further set of experiments the dose rate was increased to 0.4 mg kg-1 and mechanical testing was repeated. There was still no clinically significant elevation in pressure thresholds. At a dose rate of 0.2 mg kg-1 the drug had no detectable effect on respiratory blood gas tensions. Behavioural changes were severe if a dose rate of 0.2 mg kg-1 was exceeded.

Measurement of mechanical thresholds, plasma cortisol and catecholamines in control and lame cattle: a preliminary study.

The threshold response to a mechanical nociceptive stimulus was significantly lower on the lame hind limb of lame cows than on the same limb of sound cows. There were no significant differences between the concentrations of cortisol, noradrenaline, adrenaline or dopamine in the blood plasma of the sound and lame cows.

Effect of chronic pain associated with lameness on plasma cortisol concentrations in sheep: a field study

Plasma cortisol concentrations were measured in two groups of sheep taken from 29 flocks in north Devon. The first group were healthy adult females and the second group were adult females suffering from footrot in one forefoot. These sheep were assessed for the severity of the lesion and the level of lameness and assigned a score. The plasma cortisol concentration was significantly higher in the lame sheep than in the healthy sheep and remained so for up to three months after the apparent resolution of the clinical lesion. There was no correlation between the severity of the footrot and the concentration of plasma cortisol.

ANALGESIC EFFECTS OF DETOMIDINE IN THOROUGHBRED HORSES WITH CHRONIC TENDON INJURY

This study was undertaken to assess the analgesia provided by detomidine (20 micrograms kg-1 intravenously) in thoroughbred horses. Pain thresholds to a mechanical noxious stimulus were measured before and after a period of mild chronic pain in one foreleg. Detomidine was a good analgesic in control animals; their pain thresholds were significantly elevated for about 60 minutes. After injury, the injured leg had a significantly lower pain threshold and the intensity and duration of analgesia provided by detomidine were significantly reduced. The analgesia in the opposite (sound) leg was also reduced, indicating that there were both central and peripheral aspects to this increased sensitivity to painful stimuli. Detomidine deserves to be considered as a potent analgesic in the horse rather than a sedative with analgesic side effects.

Effects of clinically occurring chronic lameness in sheep on the concentrations of plasma noradrenaline and adrenaline

Plasma adrenaline (AD) and noradrenaline (NA) concentrations were measured by high performance liquid chromatography with electrochemical detection in blood samples from control and lame sheep. The lame sheep suffered from naturally occurring foot rot and showed behavioural characteristics normally associated with chronic pain. The lame sheep were scored both for impairment of gait and pathology of the foot and divided into mild and severely affected groups. Both the mildly and severely lame group showed a significant increase in plasma AD and plasma NA which tended to persist even after clinical resolution of the condition. The measurement of plasma AD and NA may provide information which can be used to assess animals experiencing chronic pain, when taken in conjunction with other parameters, such as nociceptive thresholds and plasma hormone levels.