Noxious Somatic Inputs to Hypothalamic‐Midbrain Projection Neurones: a Comparison of the Columnar Organisation of Somatic and Visceral Inputs to the Periaqueductal Grey in the Rat

Abstract

The induction of Fos protein was used to localise hypothalamic neurones activated by noxious somatic stimulation. This was combined with retrograde transport of fluorescent latex microspheres from identified 'pressor' and 'depressor' sites in the dorsolateral/lateral or ventrolateral columns of the periaqueductal grey (PAG). Fos-positive neurones were found throughout the rostral hypothalamus. Of those neurones activated by noxious somatic stimuli that projected to the PAG all but one was retrogradely labelled from sites that included the lateral column. Only one neurone was double labelled following injection of tracer at a depressor site in the ventrolateral PAG. This is in marked contrast to visceroresponsive hypothalamic neurones, a larger proportion of which project to the PAG and which, as reported previously, preferentially target depressor sites in the ventrolateral sector. These results are discussed in relation to the roles of the anterior hypothalamus and the different functional columns of the PAG in co-ordinating autonomic and sensory functions in response to nociceptive inputs originating in different peripheral domains.

Hypothalamic and Midbrain Circuitry That Distinguishes Between Escapable and Inescapable Pain

“…In contrast, fewer anterior hypothalamic neurons that are activated by noxious somatic stimuli project to the PAG, and those that do project almost exclusively to its dorsolateral/lateral sector (16). It would seem therefore that hypothalamic-midbrain projection neurons activated by noxious visceral or noxious somatic stimuli constitute largely separate populations of cells that innervate the ventrolateral or dorsolateral/lateral columns of the PAG, respectively.…”

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

“…The dmVMH along with other interconnected medial hypothalamic nuclei (dorsal premammillary nucleus and anteriomedial hypothalamus-medial preoptic area) constitute a hypothalamic behavioral control system that governs the execution of innate defensive responses to environmental threats (Petrovich et al, 2001;Canteras, 2002). These hypothalamic nuclei exhibit c-Fos activation following exposure to either noxious or non-noxious threatening stimuli (Bullitt, 1990;Sandner, et al, 1993;Canteras et al, 1997;Liu et al, 1998;Rodella et al, 1998;Beckett et al, 1999;Dielenberg, et al, 2001;Parry et al, 2002), and inactivation or damage of these sites blocks naturally occurring defensive behaviors (Canteras et al, 1997;Cheu and Siegel, 1998;Markham et al, 2004). Stimulation of these medial hypothalamic nuclei elicits defensive responding in rats, cats and monkeys (Fernandez de Molina and Hunsperger, 1962;Lipp and Hunsperger, 1978;Milani and Graeff, 1987), and in humans generates reports of fear, anxiety and horror (Ervin et al, 1969;Heath, 1975;Iacono and Nashold, 1982;Tasker, 1982).…”

“…The ventromedial hypothalamus (VMH) is a forebrain site implicated in generation of pain affect. The dorsomedial division of the VMH (dmVMH) receives nociceptive afferents (Bester et al, 1995;Bernard et al, 1996;Braz et al, 2005), and neural activity is evoked in dmVMH by noxious peripheral stimulation in animals (Bullitt, 1990;Parry et al, 2002). Although current neuroimaging technology does not permit identification of individual hypothalamic nuclei the medial hypothalamus is activated in humans exposed to noxious stimulation (Hsieh et al, 1996;Zubieta et al, 2001;Petrovic et al, 2004).…”

Inactivation of the periaqueductal gray attenuates antinociception elicited by stimulation of the rat medial preoptic area

“…MPOA neurons do not project directly to the spinal cord, but robustly innervate two major brainstem areas involved in descending nociceptive modulation, the periaqueductal gray (PAG) and rostroventromedial medulla (RVM) [5,12,26,29,32]. MPOA neurons are responsive to noxious somatic and visceral stimuli [30], and electrical stimulation of the cat and rat MPOA has been reported to suppress spinal cord and medullary dorsal horn neuronal responses to noxious cutaneous or visceral input [8,20,21,24]. Although these studies implicate MPOA in antinociception, there are several limitations.…”

“…Thus, the effects of MPOA stimulation may be due to direct activation of PAG or RVM neurons rather than activation of MPOA neurons. While a limited number of studies used chemical stimulation to activate MPOA neurons, conclusion were based on a limited samples and in some cases responses elicited by electrical stimulation were not replicated by chemical stimulation [21,30].…”