Contribution of the ventromedial hypothalamus to generation of the affective dimension of pain

Abstract

The ventromedial hypothalamus (VMH) is a core structure underlying the generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the dorsomedial division of the VMH (dmVMH) receives nociceptive input. The present study evaluated the contribution of the dmVMH to generation of the affective reaction to pain in rats. Noxious tailshock elicits from rats vocalization afterdischarges (VADs) that have distinct spectrographic characteristics and are a validated model of the affective reaction to pain. VAD-like vocalizations (vocalizations with the same spectral characteristics of VADs) were elicited by stimulation (electrical or chemical) of the dmVMH. Stimulation in the vicinity of the dmVMH was ineffective in eliciting VADs. Manipulation of GABA A neurochemistry within the dmVMH altered the threshold for elicitation of VADs by dmVMH stimulation or tailshock. Administration of the GABA A antagonist bicuculline or the GABA A agonist muscimol into the dmVMH lowered and elevated VAD thresholds, respectively. These treatments did not alter thresholds of other tailshock elicited responses (vocalizations during tailshock or spinal motor reflexes). Bicuculline and muscimol administered into the dmVMH also elevated and lowered the asymptotic level of fear conditioning supported by dmVMH stimulation or tailshock. These findings demonstrate that the dmVMH contributes to the processing of pain affect and that the affective dimension of pain belongs to a broader class of sensory experience that represents threat to the individual.

Nuclei-and condition-specific responses to pain in the bed nucleus of the stria terminalis

“…The neurobiological construct of the emotional aspect of pain is at the supraspinal level and more specifically involves brain regions such as the anterior cingulate cortex, the amygdala, and the BST (Borszcz, 2006;Deyama et al, 2007;Johansen et al, 2001;Neugebauer et al, 2004;Rainville et al, 1997). The BST is ideally located anatomically and functionally to receive incoming noxious information, process this information along with additional incoming neocortical (prefrontal cortex) and other limbic structure (amygdala, hippocampus) information, and relay this message to the periphery (midbrain and brainstem) (Dong et al, 2000;Dong et al, 2001a;Dong et al, 2001b;Dong and Swanson, 2003, 2004a, b, 2006a).…”

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

“…Generation of VADs is suppressed by damage of or drug treatments into forebrain sites known to contribute to production of the affective response of humans to clinical and experimental pain 8,14,26,27,36,40,51 . Additionally, the capacity of noxious tailshock to support fear conditioning is directly related to its production of VADs 5,6,9,14 .…”

“…The audio system was calibrated by determining the relation between the peak digitized output of the analog-to-digital converter and the amplitude (SPL, B Scale) of a 3.0 kHz pure tonethe approximate fundamental frequency of pain-induced vocalizations of the rat 6,9,14 . The derived function was used to convert analog-to-digital inputs to decibels (dB).…”

“…Research in this laboratory validated a rodent model of pain affect (see Discussion). Vocalization afterdischarges (VADs) occur immediately following application of noxious tailshock, are organized within the forebrain, and have distinct spectrographic characteristics compared to vocalizations that occur during shock (VDSs) 6,9,14,16 . The effects of carbachol injected into the VTA on VAD threshold was compared to its effects on tailshock elicited behaviors organized at spinal (SMR = hindlimb movements and tail flexion) and medullary (VDS) levels of the neuraxis 10,16 .…”

Participação dos receptores NK-1 dos núcleos basolateral e central da amígdala no comportamento defensivo de ratos

“…Reações comportamentais de defesa são acompanhadas de vocalizações após a estimulação elétrica da amígdala (JURGENS et al, 1967;JURGENS, 1982;CHARPENTIER, 1967;BORSZCZ, 1999BORSZCZ, , 2006. Porém a microinjeção de SP ou agonista NK-1 não produziu vocalizações, sejam audíveis ou ultrassônicas, apesar da produção de comportamentos ansiogênicos e analgesia.…”