The differential contribution of spinopetal projections to increases in vocalization and motor reflex thresholds generated by the microinjection of morphine into the periaqueductal gray.

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The parafascicular nucleus of the intralaminar thalamus is implicated in the processing of pain affect in both animals and humans. Administration of morphine into nPf results in preferential suppression of the affective reaction to noxious tailshock in rats. The involvement of the ventrolateral periaqueductal gray in mediating the antinociceptive action of morphine injected into nPf was evaluated. Vocalizations that occur after tailshock offset (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by injection of morphine into nPf. Vocalizations that occur during tailshock were suppressed to a lesser degree, whereas, spinal motor reflexes (tail flick and hindlimb movements) were unaffected by injection of morphine into nPf. Inactivation of the vPAG via the microinjection of muscimol (GABAA agonist) produced dose-dependent antagonism of morphine-induced increases in vocalization thresholds. The results demonstrate that a functional link between the nPf and vPAG in generating the antinociceptive action of morphine injected into nPf. Perspective: Microinjection of morphine into nucleus parafascicular preferentially suppressed rats’ affective reaction to noxious stimulation. This affective analgesia was reversed by inactivation of the ventrolateral periaqueductal gray. Understanding the neurobiology underlying the suppression of pain affect will provide insights into new treatments for pain and its associated affective disorders.

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Contribution of the Periaqueductal Gray to the Suppression of Pain Affect Produced by Administration of Morphine Into the Intralaminar Thalamus of Rat

Munn

Harte

Lagman

et al. 2009

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“…26–29,35,44 The failure to observe an increase in SMR threshold does not reflect the resistance of this response to antinociceptive treatments. In previous studies, administration of morphine into the rostral ventromedial medulla or ventrolateral periaqueductal gray (vlPAG) produced significant increases in SMR, VDS, and VAD thresholds 8,9,11,14 and the intrathecal administration of morphine, serotonin, or norepinephrine was equally effective in raising SMR, VDS, and VAD thresholds. 15 The capacity of these central treatments to elevate SMR threshold also demonstrates that SMRs are not generated by direct stimulation of the tail musculature.…”

Section: Discussionmentioning

confidence: 93%

NMDA or Non-NMDA Receptor Antagonism Within the Amygdaloid Central Nucleus Suppresses the Affective Dimension of Pain in Rats: Evidence for Hemispheric Synergy

Spuz

Borszcz

2012

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The amygdala contributes to generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study evaluated the contribution of glutamate receptors in CeA to generation of the affective response to acute pain in rats. Vocalizations that occur following a brief noxious tailshock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by bilateral injection into CeA of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (AP5, 1μg, 2μg, or 4μg) or the non-NMDA receptor antagonist 6-Cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, .25μg, .5μg, 1μg, or 2μg). Vocalizations that occur during tailshock were suppressed to a lesser degree, whereas, spinal motor reflexes (tail flick and hindlimb movements) were unaffected by injection of AP5 or CNQX into CeA. Unilateral administration of AP5 or CNQX into CeA of either hemisphere also selectively elevated vocalization thresholds. Bilateral administration of AP5 or CNQX produced greater increases in vocalization thresholds than the same doses of antagonists administered unilaterality into either hemisphere indicating synergistic hemispheric interactions. Perspective The amygdala contributes to production of emotional responses to environmental threats. Blocking glutamate neurotransmission within the central nucleus of the amygdala suppressed rats’ emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders.

“…The failure to observe increases in SMR threshold does not reflect the resistance of this response to antinociceptive treatments. In previous studies, administration of morphine into the rostral ventromedial medulla or ventrolateral periaqueductal gray produced significant increases in VAD, VDS, and SMR thresholds 8,12 , and the intrathecal administration of morphine, serotonin, or norepinephrine was equally effective in raising VAD, VDS, and SMR thresholds 13 . The capacity of these central treatments to elevate SMR threshold also demonstrates that SMRs are not generated by direct stimulation of the tail musculature.…”

Section: Discussionmentioning

confidence: 99%

Affective Analgesia Following Muscarinic Activation of the Ventral Tegmental Area in Rats

Kender

Harte

Munn

et al. 2008

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Cholinergic stimulation of dopamine neurons in the ventral tegmental area (VTA) underlies activation of the brain reward circuitry. Activation of this circuit is proposed to preferentially suppress the affective reaction to noxious stimulation. Vocalization afterdischarges (VADs) are a validated model of the affective response of rats to noxious tailshock. The antinociceptive action of the acetylcholine agonist carbachol microinjected into the VTA on VAD threshold was compared to its effect on the thresholds of other tailshock-elicited responses (VDS = vocalizations during shock, and SMR = spinal motor reflexes). Whereas VADs are organized within the forebrain, VDSs and SMRs are organized at medullary and spinal levels of the neuraxis, respectively. Carbachol (1 μg, 2 μg, and 4 μg) injected into VTA produced dose-dependent increases in VAD and VDS thresholds, although increases in VAD threshold were significantly greater than increases in VDS threshold. Administration of carbachol into VTA failed to elevate SMR threshold. Elevations in vocalization thresholds produced by intra-VTA carbachol were reversed in a dose-dependent manner by local administration of the muscarinic receptor antagonist atropine sulfate (30 μg and 60 μg). These results provide the first demonstration of the involvement of the VTA in muscarinic-induced suppression of pain affect.Perspective-Cholinergic activation of the brain reward circuit produced a preferential suppression of rats' affective reaction to noxious stimulation. The neurobiology that relates reinforcement to suppression of pain affect may provide insights into new treatments for pain and its associated affective disorders.