Central Amygdala Metabotropic Glutamate Receptor 5 in the Modulation of Visceral Pain

Crock, Lara W.; Kolber, Benedict J.; Morgan, Clinton D.; Sadler, Katelyn E.; Vogt, Sherri K.; Bruchas, Michael R.; Gereau, Robert W.

doi:10.1523/jneurosci.1473-12.2012

Cited by 101 publications

(87 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, ROS scavengers in the amygdala can inhibit increased pain behaviors [25;36;40]. These findings are consistent with an important role of G protein-coupled mGluR5 in amygdala plasticity in pain [9;21;32;35;45] and with an emerging role of ROS in peripheral [28;55;60], spinal [15;22;29;30;33;34;52;54;61], and supraspinal [25;36;39;40;48] mechanisms of inflammatory and neuropathic pain.…”

Section: Discussionsupporting

confidence: 61%

Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Kim

Thompson

et al. 2017

PAIN

View full text Add to dashboard Cite

Neuroplasticity in the amygdala, a brain center for emotions, leads to increased neuronal activity and output that can generate emotional-affective behaviors and modulate nocifensive responses. Mechanisms of increased activity in the amygdala output region (central nucleus, CeA) include increased reactive oxygen species, and so we explored beneficial effects of monomethyl fumarate (MMF), which can have neuroprotective effects through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) anti-oxidant response pathway. Systemic (intraperitoneal) MMF dose-dependently inhibited vocalizations and mechano-sensitivity (hindlimb withdrawal reflexes) of rats in an arthritis pain model (kaolin/carrageenan-induced mono-arthritis in the knee). Stereotaxic administration of MMF into the CeA by microdialysis also inhibited vocalizations but had a limited effect on mechano-sensitivity, suggesting a differential contribution to emotional-affective versus sensory pain aspects. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that stereotaxic administration of MMF into the CeA by microdialysis inhibited background activity and responses of CeA neurons to knee joint stimulation in the arthritis pain model. MMF had no effect on behaviors and neuronal activity under normal conditions. The results suggest that MMF can inhibit emotional-affective responses in an arthritis pain model through an action that involves the amygdala (CeA).

show abstract

Section: Discussionsupporting

confidence: 61%

Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Kim

Thompson

et al. 2017

PAIN

View full text Add to dashboard Cite

show abstract

“…As a preliminary indicator of bladder pain involvement in rodents, increased levels of cFos protein were observed in the CeA following a single CYP injection 22 . In an opposing top-down approach, non-specific optogenetic activation of the right CeA resulted in increased pain-like responses during bladder distension, demonstrating this loci's ability to modulate sensory information arising from the viscera 23 .…”

Section: Resultsmentioning

confidence: 97%

“…Administration of agonists and antagonists of metabotropic glutamate receptor 5 (mGluR5) into the CeA increase and decrease UBD-evoked pain-like responses respectively by altering CeA neuronal excitability 23 . Furthermore, genetic disruption of mGluR5 in the right CeA decreases both bladder pain and dorsal horn spinal phosphorylation of extracellular signal-regulated kinase (ERK), a common marker of nociceptive-induced neuronal activation, following UBD 23 . Asymmetrical involvement of the left and right CeA in somatic pain processing has been reported, but the specific contribution of the left CeA in bladder pain remains unknown 24 .…”

Section: Resultsmentioning

confidence: 99%

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Sadler

Kolber

2016

Journal of Urology

View full text Add to dashboard Cite

Purpose Chronic bladder pain is a debilitating condition often accompanied by alterations in affective and autonomic function. Many of the symptoms associated with chronic bladder pain are mediated by the central nervous system. In this review, data from preclinical animal models and human neuroimaging studies were analyzed and a theoretical supraspinal bladder pain network was generated. Materials and Methods A comprehensive literature review was performed using PubMed and Google Scholar. Relevant reviews, original research articles, and their cited references were summarized then organized on a neuroanatomical basis. Results The following brain loci are the most predominant in the bladder pain literature: thalamus, parabrachial nucleus, cerebral cortex, amygdala, hypothalamus, periaqueductal gray, and rostral ventromedial medulla. This review highlights each of these regions, discussing the molecular and physiological changes that occur in each during the context of bladder pain. Conclusions A complex network of brain loci is involved in bladder pain modulation. Studying these brain regions and the changes they undergo during the transition from acute to chronic bladder pain will provide novel therapeutic strategies for those suffering from chronic bladder pain diseases such as interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

show abstract

“…The effects of CeA manipulations on nociception are likely dictated by whether these manipulations affect interneurons or projection neurons or both, and also by the extent and laterality of the lesion. For example, one prior study showed that unilateral optogenetic activation of right CeA promotes nociception in a mouse model of chronic bladder pain (Crock et al, 2012), whereas other work shows that bilateral CeA lesion blocks antinociception (ie, promotes nociception; Werka, 1994;Werka and Marek, 1990). In humans with PTSD, neuroimaging studies report higher amygdala activity at rest (Semple et al, 2000), and hyper-reactivity of the amygdala to traumarelated stimuli (Dickie et al, 2008;Morey et al, 2009;Rauch et al, 2000), although those studies lacked the resolution to isolate the CeA.…”

Section: Discussionmentioning

confidence: 99%

Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

Itoga

Hellard

Whitaker

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stressinduced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

show abstract

Central Amygdala Metabotropic Glutamate Receptor 5 in the Modulation of Visceral Pain

Cited by 101 publications

References 43 publications

Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model

Urine Trouble: Alterations in Brain Function Associated with Bladder Pain

Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

Contact Info

Product

Resources

About