Corticotropin-Releasing Factor in the Rat Amygdala Differentially Influences Sensory-Discriminative and Emotional-like Pain Response in Peripheral Neuropathy

Bourbia, Nora; Ansah, Osei B.; Pertovaara, Antti

doi:10.1016/j.jpain.2010.05.004

Cited by 32 publications

(28 citation statements)

References 38 publications

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“…CRF2 receptor-mediated inhibition does not reach behavioral significance since astressin-2B had no significant effect on pain behaviors (Fu and Neugebauer 2008). In a neuropathic pain model (spared nerve injury) a non-selective CRF receptor antagonist (CRF 9-41 ) had no effect on emotional-affective (aversive place-conditioning test) and nocifensive (hindlimb-withdrawal thresholds) pain behaviors (Bourbia et al 2010). Increasing endogenous CRF in the CeA with a CRF-binding protein inhibitor (CRF 6–33 ) had mixed effects, facilitating nocifensive responses while attenuating emotional-affective behaviors (Bourbia et al 2010).…”

Section: Pharmacology Of Pain-related Processing In the Amygdalamentioning

confidence: 99%

“…In a neuropathic pain model (spared nerve injury) a non-selective CRF receptor antagonist (CRF 9-41 ) had no effect on emotional-affective (aversive place-conditioning test) and nocifensive (hindlimb-withdrawal thresholds) pain behaviors (Bourbia et al 2010). Increasing endogenous CRF in the CeA with a CRF-binding protein inhibitor (CRF 6–33 ) had mixed effects, facilitating nocifensive responses while attenuating emotional-affective behaviors (Bourbia et al 2010). Microinjections of a CRF receptor antagonist (CRF 9-41 ) into the CeA reduced hyperalgesia (tail flick test) associated with morphine withdrawal but had no effect in normal controls (McNally and Akil 2002).…”

Section: Pharmacology Of Pain-related Processing In the Amygdalamentioning

confidence: 99%

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Amygdala Pain Mechanisms

Neugebauer

2015

Handbook of Experimental Pharmacology

318

342

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A limbic brain area the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms.

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Section: Pharmacology Of Pain-related Processing In the Amygdalamentioning

confidence: 99%

Section: Pharmacology Of Pain-related Processing In the Amygdalamentioning

confidence: 99%

Amygdala Pain Mechanisms

Neugebauer

2015

Handbook of Experimental Pharmacology

318

342

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“…CRF release in the CeAmy causes hypersensitivity via CRF1 receptor and analgesia via CRF2 receptor [17-19]. While low doses of endogenous CRF in CeAmy increase pain sensitivity [20], high doses of exogenous CRF are analgesic [21]. One hypothesis that summarizes the role of CRF in pain processing is that the CRF neurons in the amygdala may act as an on/off switch for chronic pain [22].…”

Section: Introductionmentioning

confidence: 99%

Contribution of amygdala CRF neurons to chronic pain

Andreoli

Marketkar

Dimitrov

2017

Experimental Neurology

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We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over-activation of amygdala CRF neurons is very likely an important contributing factor for pain chronification.

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“…In addition, hyperalgesic effects, painrelated synaptic facilitation, increased excitability, and increased pain behavior were reported in the several animal pain models (Taché et al 2005;Fu & Neugebauer 2008). For example, Bourbia et al (2010) have demonstrated that microinjection with CRH into central nucleus of the amygdale produces an enhancement of mechanical hypersensitivity in spared nerve ligation model. To examine the role of CRHR1 in the regulation of nociception, we used CRHR1 +/− mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that activation of CRHR1 receptor in the amygdala contributes to pain-related synaptic facilitation, increased excitability, and pain behavior (Fu & Neugebauer 2008). Bourbia et al (2010) have demonstrated that microinjection with CRH into central nucleus of the amygdale produces an enhancement of mechanical hypersensitivity in spared nerve ligation model. Although the activation of CRH receptors could induce both analgesia and hyperalgesia, the exact role of CRHR1 in the regulation of nociception has not been well characterized.…”

Section: Introductionmentioning

confidence: 99%

Role of corticotropin-releasing hormone receptor 1 in the regulation of nociception in mice

Park

Choi

Sim

et al. 2014

Animal Cells and Systems

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Corticotropin-releasing hormone (CRH) is known to be involved in both antinociceptive and nociceptive processing. In the present study, we examined the role of the CRH receptor 1 in the regulation of nociception in mice. First, we found that CRH mRNA level was elevated in the hypothalamus or hippocampus by intraperitoneal (i.p.) injection with 1% acetic acid, intraplantar injection of 5% formalin, or intrathecal (i.t.) injection of substance P (0.7 μg/5 μl). Nociceptive behavior induced by acetic acid, formalin, or substance P were reduced in CRHR1 heterozygous (CRHR1 +/− ) mice compared to that in C57BL6 (wild type, CRHR1 +/+ ) mice group. Furthermore, administration with CRHR1 antagonists such as CP 154526 (10 mg/kg, i.p.) or α-helical CRF 9-41 (10 μg/5 μl, intracerebroventricular [i.c.v.]) attenuated nociceptive behaviors observed in the substance P and writhing pain models. Our results suggest that CRHR1 might play an important role in the regulation of nociception, especially, toward nociceptive activation rather than producing the antinociception.

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Corticotropin-Releasing Factor in the Rat Amygdala Differentially Influences Sensory-Discriminative and Emotional-like Pain Response in Peripheral Neuropathy

Cited by 32 publications

References 38 publications

Amygdala Pain Mechanisms

Amygdala Pain Mechanisms

Contribution of amygdala CRF neurons to chronic pain

Role of corticotropin-releasing hormone receptor 1 in the regulation of nociception in mice

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