Some inhibitory neurons in the spinal cord develop c-fos-immunoreactivity after noxious stimulation

Todd, Andrew J.; Spike, Rosemary C.; Brodbelt, Andrew; Price, RF; Shehab, Safa

doi:10.1016/0306-4522(94)90525-8

Cited by 86 publications

(45 citation statements)

References 55 publications

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“…To test this hypothesis, we investigated the coexpression of KOR and c-Fos (as a marker of neuronal activation) 1 hour after either intraplantar formalin or intraperitoneal acetic acid. The distribution of c-Fos immunoreactivity after formalin administration was similar to that observed in previous studies (Presley et al, 1990;Todd et al, 1994). Within the superficial dorsal horn, labeled cells were clustered medially in L3-L5, ipsilateral to the injection.…”

Section: Resultssupporting

confidence: 87%

Sex, Pain, and Opioids: Interdependent Influences of Sex and Pain Modality on Dynorphin-Mediated Antinociception in Rats

Liu¹,

Schnell²,

Wessendorf³

et al. 2012

J Pharmacol Exp Ther

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The role of dynorphin A (1-17; Dyn) and its associated kappa opioid receptor (KOR) in nociception represents a longstanding scientific conundrum: Dyn and KOR (Dyn/KOR) have variously been reported to inhibit, facilitate, or have no effect on pain. We investigated whether interactions between sex and pain type (which are usually ignored) influenced Dyn/ KOR-mediated antinociception. Blockade of the spinal a 2 -noradrenergic receptor (a 2 -NAR) using yohimbine elicited comparable spinal Dyn release in females and males. Nevertheless, the yohimbine-induced antinociception exhibited sexual dimorphism that depended on the pain test used: in the intraperitoneal acetic acid-induced writhing test, yohimbine produced antinociception only in females, whereas in the intraplantar formalin-induced paw flinch test, antinociception was observed only in males. In females and males, both intrathecal Dyn antibodies and spinal KOR blockade eliminated the yohimbine-induced antinociception, indicating that Dyn/ KOR mediated it. However, despite the conditional nature of spinal Dyn/KOR-mediated yohimbine antinociception, both intraplantar formalin and intraperitoneal acetic acid activated spinal Dyn neurons that expressed a 2 -NARs. Moreover, Dyn terminals apposed KOR-expressing spinal nociceptive neurons in both sexes. This similar organization suggests that the sexually dimorphic interdependent effects of sex and pain type may result from the presence of nonfunctional (silent) KORs on nociceptive spinal neurons that are responsive to intraplantar formalin (in females) versus intraperitoneal acetic acid (in males). Our findings that spinal Dyn/KORmediated antinociception depends on interactions between sex and pain type underscore the importance of using both sexes and multiple pain models when investigating Dyn/KOR antinociception.

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Section: Resultssupporting

confidence: 87%

Sex, Pain, and Opioids: Interdependent Influences of Sex and Pain Modality on Dynorphin-Mediated Antinociception in Rats

Liu¹,

Schnell²,

Wessendorf³

et al. 2012

J Pharmacol Exp Ther

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“…As afferents innervating different deep somatic structures share a common laminar pattern of spinal termination, it is not surprising that the distribution of Fos-like IR neurons following i.m. formalin injections into gastrocnemius/ soleus (i.e., predominantly superficial dorsal horn, with significant, but fewer numbers of labeled neurons in deep dorsal horn, intermediate and ventral grey, lamina X, and the nucleus of the DLF) was similar to that of studies utilising other noxious deep somatic manipulations (Me- , 1989;Herdegen et al, 1991;Abbadie et al, 1992;Lima et al, 1993;McKitrick and Calaresu, 1993;Sugimoto et al, 1993;Todd et al, 1994;Honoré et al, 1996). Following i.m.…”

Section: Spino-pag Afferents and Deep Painmentioning

confidence: 60%

Spinal sources of noxious visceral and noxious deep somatic afferent drive onto the ventrolateral periaqueductal gray of the rat

et al. 2000

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Studies utilizing the expression of Fos protein as a marker of neuronal activation have revealed that pain of deep somatic or visceral origin selectively activates the ventrolateral periaqueductal gray (vlPAG). Previous anatomical tracing studies revealed that spinal afferents to the vlPAG arose from the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus at all spinal segmental levels, with approximately 50% of vlPAG-projecting spinal neurons found within the upper cervical spinal cord. This study utilized detection of Fos protein to determine the specific populations of vlPAG-projecting spinal neurons activated by noxious deep somatic or noxious visceral stimulation. Pain of cardiac or peritoneal (i.e., visceral) origin activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the thoracic cord, whereas pain of hindlimb (i.e., deep somatic) origin activated neurons in the same laminar regions but in the lumbosacral cord. Each of these deep noxious manipulations also activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the upper cervical spinal cord. In a second set of experiments, the combination of retrograde tracing and Fos immunohistochemistry revealed that vlPAG-projecting spinal neurons activated by deep somatic pain were located in both the upper cervical and lumbosacral cord, whereas those activated by visceral pain were restricted to the thoracic spinal cord. Thus pain arising from visceral versus deep somatic body regions influences neural activity within the vlPAG via distinct spinal pathways. The findings also highlight the potential significance of the upper cervical cord in integrating pain arising from deep structures throughout the body.

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“…However, some noxious inputs by means of ligation and urethral occlusion cannot be excluded. These inputs would be reflected by an increase in fos-I nuclei in the superficial dorsal horn (Menetrey et al, 1989;Birder and de Groat, 1993;Todd et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Identification of spinal neurons involved in the urethrogenital reflex in the female rat

Marson

Cai

Makhanova

2003

J of Comparative Neurology

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The urethrogenital (UG) reflex is a spinal sexual reflex that consists of autonomic and somatic nerve activity and vaginal, uterine, and anal sphincter contractions. The UG reflex is under tonic descending inhibition by neurons in the region of the nucleus paragigantocellularis (nPGi). The location of spinal neurons activated by the UG reflex was examined in the female rat using the immediate early gene, c-fos. In addition, the descending inputs from the nPGi onto fos-activated neurons was examined using the anterograde tracer biotin dextran amine injected into the nPGi. The UG reflex resulted in a significant increase in fos-positive nuclei in segments T12-S1, compared with experimental controls in which the UG reflex was not activated. Spinal circuits involved in the UG reflex include neurons relaying afferent information from the pudendal sensory nerve, in the dorsal horn and medial cord of L5-S1. Efferent output includes preganglionic neurons located in the lateral gray of L5-S1 and lateral and medial gray of T13-L2. Spinal interneurons involved in the UG reflex were found close to the preganglionic neurons and in the dorsal horn and intermediate and medial gray of T12-S1. NPGi inputs were found primarily on the autonomic efferents and interneurons in the medial and intermediate gray. These studies demonstrate multisegmental spinal circuits activated with the UG reflex and demonstrate that the descending inhibition from the nPGi is by means of preganglionic and somatic efferents and spinal interneurons closely associated with the efferent output.

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Some inhibitory neurons in the spinal cord develop c-fos-immunoreactivity after noxious stimulation

Cited by 86 publications

References 55 publications

Sex, Pain, and Opioids: Interdependent Influences of Sex and Pain Modality on Dynorphin-Mediated Antinociception in Rats

Sex, Pain, and Opioids: Interdependent Influences of Sex and Pain Modality on Dynorphin-Mediated Antinociception in Rats

Spinal sources of noxious visceral and noxious deep somatic afferent drive onto the ventrolateral periaqueductal gray of the rat

Identification of spinal neurons involved in the urethrogenital reflex in the female rat

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