Abstract
The central nucleus of the amygdala (CeA) is involved in processing and regulation
of pain. We determined whether amygdaloid corticotropin-releasing factor (CRF) contributes
to pain modulation in the neuropathic rat. Emotional aspect of pain was assessed by
an aversive place-conditioning test and sensory aspect of pain by determining monofilament-induced
limb-withdrawal threshold. CRF6-33 (an inhibitor of CRF-binding protein) or CRF9-41, a nonselective CRF receptor antagonist, was microinjected to the left or right CeA
or a control site in rats with spared nerve injury (SNI) or sham operation of the
left hind limb. In SNI animals, CRF6-33 in the left or right CeA, but not in a control site, attenuated emotional painlike
behavior and increased sensory pain. In sham controls, CRF6-33 in the right but not left CeA increased sensory aspect of pain, without influence
on place-avoidance behavior. The effects induced by CRF6-33 were reversed by CRF9-41. The results indicate that endogenous CRF in the CeA, through action on CRF receptors,
may differentially influence emotional and sensory aspects of pain in neuropathy.
While the right CeA had a dominant role in modulation of pain-related responses in
sham controls, left as well as right CeA contributed to pain modulation in neuropathic
animals.
Perspective
An increase in free endogenous corticotropin-releasing factor in the central nucleus
of the amygdala was accompanied by increased cutaneous hypersensitivity and decreased
emotional painlike behavior in neuropathic animals. This finding indicates that CRF
in the amygdala may have differential effects on sensory and emotional aspects of
neuropathic pain.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Brain afferents to the medullary dorsal reticular nucleus: A retrograde and anterograde tracing study in the rat.Eur J Neurosci. 2002; 16: 81-95
- Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals.Exp Neurol. 2009; 216: 66-74
- Influence of amygdaloid glutamatergic receptors on sensory and emotional pain-related behavior in the neuropathic rat.Behav Brain Res. 2010; 209: 174-178
- The effects of CRF and the urocortins on [3H]GABA release from the rat amygdala—An in vitro superfusion study.Brain Res Bull. 2008; 75: 15-17
- Corticotropin releasing factor (CRF) binding protein: A novel regulator of CRF and related peptides.Front Neuroendocrinol. 1995; 16: 362-382
- Nucleus centralis of the amygdala and the globus pallidus ventralis: Electrophysiological evidence for an involvement in pain processes.J Neurophysiol. 1992; 68: 551-569
- Projections from the nociceptive area of the central nucleus of the amygdala to the forebrain: A PHA-L study in the rat.Eur J Neurosci. 2001; 14: 229-255
- 4th: Hemispheric lateralization of a molecular signal for pain modulation in the amygdala.Mol Pain. 2008; 4: 24
- Role of corticotropin-releasing factor and its receptor in nociceptive modulation in the central nucleus of amygdala in rats.Brain Res. 2004; 995: 23-28
- Spared nerve injury: An animal model of persistent peripheral neuropathic pain.Pain. 2000; 87: 149-158
- Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior.J Neurosci. 2008; 28: 3861-3876
- Pain pathways and parabrachial circuits in the rat.Exp Physiol. 2002; 87: 251-258
- Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of peripheral neuropathy.Eur J Neurosci. 2007; 26: 2188-2195
- Neuropathic pain is associated with depressive behaviour and induces neuroplasticity in the amygdala of the rat.Exp Neurol. 2008; 213: 48-56
- Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin-releasing factor receptor ligands in rats.Behav Brain Res. 2001; 122: 43-50
- NMDA receptor-independent synaptic plasticity in the central amygdala in the rat model of neuropathic pain.Pain. 2007; 127: 161-172
- Differential effects of CRF1 and CRF2 receptor antagonists on pain-related sensitization of neurons in the central nucleus of the amygdala.J Neuyrophysiol. 2007; 97: 3893-3904
- Pro- and anti-nociceptive effects of corticotropin-releasing factor (CRF) in central amygdala neurons are mediated through different receptors.J Neurophysiol. 2008; 99: 1201-1212
- Hemispheric lateralization of pain processing by amygdala neurons.J Neurophysiol. 2009; 102: 2253-2264
- Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala.Mol Pain. 2007; 3: 13
- Regulation of corticotropin-releasing factor-binding protein expression in amygdalar neuronal cultures.J Neuroendocrinol. 2009; 11: 959-966
- Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat.Pain. 1998; 74: 55-59
- A behavioral test paradigm to measure the aversive quality of inflammatory and neuropathic pain in rats.Exp Neurol. 2000; 163: 490-494
- The role of corticotropin-releasing factor in pain and analgesia.Pain. 2000; 84: 1-12
- The impact of age on emotional and cognitive behaviours triggered by experimental neuropathy in rats.Pain. 2009; 144: 57-65
- The medullary dorsal reticular nucleus as a pronociceptive centre of the pain control system.Prog Neurobiol. 2002; 66: 81-108
- Coordinate and divergent regulation of corticotropin-releasing factor (CRF) and CRF-binding protein expression in an immortalized amygdalar neuronal cell line.Endocrinology. 1999; 140: 251-259
- Injection of solutions into cerebral tissue: Relation between volume and diffusion.Physiol Behav. 1966; 1: 171-174
- Subcortical processing of nociceptive information: Basal ganglia and amygdala.in: Cervero F. Jensen T.S. Handbook of Clinical Neurology Vol. 81. Elsevier, Amsterdam, NL2006: 141-158
- The amygdala and persistent pain.Neuroscientist. 2004; 10: 221-234
- Forebrain pain mechanisms.Brain Res Rev. 2009; 60: 226-242
- Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behavior.Neuropharmacology. 2008; 55: 537-545
- The Rat Brain in Stereotaxic Coordinates.4th ed. Academic Press, New York, NY1998
- Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective motivational pain responses in a rat model of peripheral nerve injury.Pain. 2007; 127: 17-26
- The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.Proc Natl Acad Sci U S A. 1992; 89: 4192-4196
- Corticotropin-releasing factor in the basolateral amygdala enhances memory consolidation via an interaction with the β-adrenoreceptor-cAMP pathway: Dependence on glucocorticoid receptor activation.J Neurosci. 2008; 28: 6642-6651
- Electron microscopic localization of corticotropin-releasing factor (CRF) and CRF receptor in rat and mouse central nucleus of the amygdala.J Comp Neurol. 2009; 512: 323-335
- Limbic and HPA axis function in an animal model of chronic neuropathic pain.Physiol Behav. 2006; 88: 67-76
- Influence of peripheral nerve injury on response properties of locus coeruleus neurons and coeruleospinal antinociception in the rat.Neuroscience. 2007; 146: 1785-1794
Article info
Publication history
Published online: July 12, 2010
Accepted:
May 18,
2010
Received in revised form:
May 18,
2010
Received:
June 16,
2009
Footnotes
Supported by grants from the Academy of Finland and the Sigrid Jusélius Foundation, Helsinki, Finland. NB was supported in part by the European Union Erasmus Programme and the Center for International Mobility (CIMO), Helsinki, Finland.
Identification
Copyright
© 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.