Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA) in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol) and morphine (2.2 nmol) into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh) that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10) was blocked by previous administration of atropine (0.7 nmol; N = 7) or naloxone (1.3 nmol; N = 7) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9) into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11). All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.

Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig.

Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA) in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol) and morphine (2.2 nmol) into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh) that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10) was blocked by previous administration of atropine (0.7 nmol; N = 7) or naloxone (1.3 nmol; N = 7) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9) into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11). All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.

Endogenous opiate analgesia induced by tonic immobility in guinea pigs.

A function of the endogenous analgesic system is to prevent recuperative behaviors generated by tissue damage, thus preventing the emission of species-specific defensive behaviors. Activation of intrinsic nociception is fundamental for the maintenance of the behavioral strategy adopted. Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. We studied the effect of TI behavior on nociception produced by the formalin and hot-plate tests in guinea pigs. The induction of TI produced a significant decrease in the number of flinches (18 +/- 6 and 2 +/- 1 in phases 1 and 2) and lickings (6 +/- 2 and 1 +/- 1 in phases 1 and 2) in the formalin test when compared with control (75 +/- 13 and 22 +/- 6 flinches in phases 1 and 2; 28 +/- 7 and 17 +/- 7 lickings in phases 1 and 2). In the hot-plate test our results also showed antinociceptive effects of TI, with an increase in the index of analgesia 30 and 45 min after the induction of TI (0.67 +/- 0.1 and 0.53 +/- 0.13, respectively) when compared with control (-0.10 +/- 0.08 at 30 min and -0.09 +/- 0.09 at 45 min). These effects were reversed by pretreatment with naloxone (1 mg/kg, ip), suggesting that the hypoalgesia observed after induction of TI behavior, as evaluated by the algesimetric formalin and hot-plate tests, is due to activation of endogenous analgesic mechanisms involving opioid synapses.

Endogenous opiate analgesia induced by tonic immobility in guinea pigs

A function of the endogenous analgesic system is to prevent recuperative behaviors generated by tissue damage, thus preventing the emission of species-specific defensive behaviors. Activation of intrinsic nociception is fundamental for the maintenance of the behavioral strategy adopted. Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. We studied the effect of TI behavior on nociception produced by the formalin and hot-plate tests in guinea pigs. The induction of TI produced a significant decrease in the number of flinches (18 + or - 6 and 2 + or - 1 in phases 1 and 2) and lickings (6 + or - 2 and 1 + or - 1 in phases 1 and 2) in the formalin test when compared with control (75 + or - 13 and 22 + or - 6 flinches in phases 1 and 2; 28 + or - 7 and 17 + or - 7 lickings in phases 1 and 2). In the hot-plate test our results also showed antinociceptive effects of TI, with an increase in the index of analgesia 30 and 45 min after the induction of TI (0.67 0.1 and 0.53 + or - 0.13, respectively) when compared with control (-0.10 + or - 0.08 at 30 min and -0.09 0.09 at 45 min). These effects were reversed by pretreatment with naloxone (1 mg/kg, ip), suggesting that the hypoalgesia observed after induction of TI behavior, as evaluated by the algesimetric formalin and hot-plate tests, is due to activation of endogenous analgesic mechanisms involving opioid synapses

Dental pain and sleep. Experimental study on guinea pigs (Cavia porcellus).

The relationship between pain and sleep was studied by using electrocorticograms (ECoG) taken from guinea pigs submitted to noxious stimulation (NS) of the dental pulp of the upper incisors, after local application of serotonin (5-HT) to the obex (a brain region inductive to sleep). The results showed that the dental electrical stimulation of the sleepy animal was capable of keeping this animal in a state of vigilance and excitation, suggesting that the trigeminal system probably acts on the sleep regulating centers.

Origin of the telencephalic spindles of the toad Bufo paracnemis

Spindles (8-11 Hz and up to 100 uV in amplitude) recorded on the surface of the surface of the telencephalic hemispheres and olfaactory bulbs of the conscious toad disappear after transection between these two structures, indicating that their presence depends onm the integrity of their interconnections. Spindles continue to be present, although in reduced numbers, after transection between the hemispheres and the diencephalon, indicating that caudal regions are not essential for generating spindles but modulate the neurons responsible for spindle genesis. In contrast, the olfactoryy nerves, in addition to their known phasis activity on the spindles, exert a tonic action since after their section there is a change in the duration and amplitude of component waves

Disruptive effect of the mesencephalic reticular formation on tonic immobility in guinea pigs.

Cholinergic stimulation of the mesencephalic reticular formation with carbachol impairs the induction of tonic immobility (TI) by restraining maneuvers and reduces the duration of immobility episodes in guinea pigs. This finding apparently disagrees with the hypothesis that environmental monitoring occurs during TI which permits the animal to evaluate the best time for escape. It is possible that this monitoring involves circuits and neurotransmitters other than the ascending cholinergic system originating in the mesencephalic reticular formation.

Disruptive effect of the mesencephalic reticular formation on tonic immobility in guinea pigs

Cholinergic stimulation of the mesencephalic reticular formation with carbachol impairs the induction of tonic immobility (TI) by restreining maneuvers and reduces the duration of immobility episodes in guiena pigs TI which permits the animal to evaluate the best6 time for escape. It is possible that this monitoring inolves cirucits and neurotransmitters other than the ascending cholinergic system origination in the mesencephalic reticular formation