Effect of morphine on air-puff-induced hyperalgesia measured by 22 kHz ultrasonic vocalization following intracerebroventricular administration of E. coli lipopolysaccharide in the rat

N. Tremblay, J. Martino, A. Dray and D. Ménard

Department of Pharmacology, AstraZeneca Inc., Montréal, Canada

Human pain is characterized by an important affective component that has not been modeled by animal studies. Vivian & Miczek (1998) suggested that 22 kHz ultrasonic vocalization (USV) in rats might communicate affective states. This could be used to measure complex animal behavior such as pain. The goal of the present study was to develop a model of hyperalgesia in which USV could be used to quantify pain. We have demonstrated that the USV pattern of naďve animals can be modulated by hyperalgesia/allodynia and that this state can be reversed by analgesics such as morphine.

In our study, animals were rendered hyperalgesic by the intracerebroventricular (i.c.v.) administration of 2.4 µg of E. coli lipopolysaccharide (LPS) [2]. Four hours following LPS injection, each animal was isolated in a sound attenuated chamber (BRS-LVE Tech Serv) and USV was elicited by the presentation of 10 standardized air-puffs (intensity=75 psi; duration=0.2 s) aversive stimuli. USV was detected with a 1.20 cm microphone (G.R.A.S. VedBaek) and the recording period lasted for 10 minutes starting with the first stimulus presentation. A commercial automated signal-detection system (Leuven Measurement System, CADA-X 3.5B) was used to analyze the recordings for each animal and to perform statistical manipulation of the data for the characterization of the USV.

Compared to naive rats, rats injected with LPS had a lower threshold for activation of USV as shown by the number of air-puff stimuli needed to induce USV and a shorter latency to obtain the first USV signal. When animals vocalized, the rate of USV as well as the number of USVs produced, increased in LPS-injected animals compared to naive rats. Also, morphine (2.5-10 µmol/kg) injected subcutaneously reversed the USV response. In summary, air-puff stimulation reliably evoked USV in pre-treated animals with LPS. This provided a robust background of distress signaling which was interpreted to be aversive and possibly hyperalgesic. In keeping with this, the opioid analgesic, morphine, attenuated USV at doses reported to be analgesic by more conventional measures of motor reflex behavior.

References

  1. Vivian, J.A.; Miczek, K.A. (1998). Effects of mu and delta opioid agonists and antagonists on affective vocal and reflexive pain responses during social stress in rats. ,i>Psychopharmacology, 139, 364-375.
  2. Walker, K.; Dray, A.; Perkins, M. (1996). Hyperalgesia in rats following intracerebroventricular administration of endotoxin: effect of bradykinin B1 and B2 receptor antagonist treatment. Pain, 65, 211-219.

Poster presented at Measuring Behavior 2000, 3rd International Conference on Methods and Techniques in Behavioral Research, 15-18 August 2000, Nijmegen, The Netherlands

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