During the action of nociceptive stimuli of varied nature the secretion of different peptides and, in particular, of somatostatin and substance P, has been demonstrated at the level of relay neurons of the spinal cord [7], and certain peptides, notably neurotensin and ca!citonin, have been shown to have a selective analgesic action, depending either on the nature of the nociceptive stimulation [3] or on its localization [4]. Angiotensin II and bombesin, which are endogenous nonopioid peptides [5, 8], are widely represented in structures of the CNS and, in particular, in the region of the posterior horn of the spinal cord, the brain stem, thalamus, and so on, and also in the descending supraspinal tracts running to the posterior horn [6]. This indicates their possible participation in the physiological mechanisms of modification of nociceptive sensation, and differences in their localization both with each other and with the opioid peptides have given rise to the suggestion that they may have different influences on nociception depending on the genesis or location of the nociceptive stimulation. In the investigation described below two types of nociceptive stimulation were studied: electrocutaneous and electrodental, for differences in their perception are well known from clinical practice. Since the most adequate parameter of nociception in animals is a change in evoked potentials (EP) of brain structures [2], and because of the considerations expressed above, the aim of the present investigation was to study the action of angiotensin II and bombesin on changes in somatosensory cortical EP of rabbits in response to electrodental and electrodermal nociceptive stimulation. EXPERIMENTAL METHOD Experiments were carried out on 40 conscious and loosely restrained make chinchilla rabbits weighing 2.5-3 kg, previously scalped under procaine anesthesia. EP were recorded from the surface of the cranial bones in the region of the somatosensory cortex in response to electrocutaneous stimulation of the contralateral hind limb (ECS), causing limb withdrawal, and electrodental stimulation (EDS), causing a licking reflex, which could be produced with the aid of electrodes inserted into the pulp of the upper incisors (sinBle square pulses, 0.5 msec, 4-20 mA). One animal was used in each experiment. By means of a cannula fixed beforehand to the skull, a solution of bombesin (from "Serva") in a dose of 20 ~g/kg (14 experiments), and a solution of angiotensin II (A II) in a dose of 50 mg/kg ("Sigma") (20 experiments), were injected in a volume of i0 ~I into the third ventricle; naloxone ("Endo") was injected ina dose of 0.15 mg/kg in a volume of 1 ml intravenoulsy (six experiments). EP were analyzed on an NTA-1024 amplitude-phase analyzer in I0 realizations. The amplitude of the component (AC) P2o-~o of EP, the one most associated with nociception [2], was determined in the animals in the initial state and at 10-min intervals after injection of the peptides. For each experiment the average background values of AC of P2o-~o of EP were determined, and taking this value as 100%, deviations at different times were calculated. The significance of differences between the results was estimated by nonparametric statistical tests and by StudentTs test.
Read full abstract