Abstract
In contrast to a classic view that the brain was a passive receiver of the pain message, Melzack and Wall proposed in 1965 that the brain exerted descending control upon spinal nociceptive transmission. This chapter reviews the substrates mediating endogenous pain-modulation. The respective roles of the ventrolateral periaqueductal gray (vlPAG) and rostroventromedial medualla (RVM) in the mediation of not only pain-inhibitory, but also pain-facilitatory responses are described behaviorally, neuroanatomically, neurochemically and neurophysiologically. How this intrinsic pain-modulatory system is activated by other brain nuclei (limbic system and cortex) and by exogeneous environmental factors is described. The emergence of sex differences and neurohormonal factors in mediating pain modulation is also considered. The neurophysiological underpinnings of RVM "ON-" and "OFF-cells" and their respective roles in endogenous pain-facilitatory and pain-inhibitory responses are discussed in detail. Finally, how these pain-modulatory responses relate to other neurobehavioral adapatations are considered, including how animal studies can inform human pain conditions and their detection through functional imaging.
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- AS ODN:
-
Antisense oligodeoxynucleotide
- CCK:
-
Cholecystokinin
- CPM:
-
Conditioned pain modulation
- CRF:
-
Corticotropin releasing factor
- DAMGO:
-
[D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin
- DNIC:
-
Diffuse noxious inhibitory controls
- DOPAC:
-
3,4-Dihydroxyphenylacetic acid, a dopamine metabolite
- DPDPE:
-
[D-Pen2,D-Pen5]Enkephalin
- β-FNA:
-
β-funaltrexamine
- HPA:
-
Hypothalamo-pituitary axis
- 5HT:
-
5-hydroxytryptamine (serotonin)
- M6G:
-
Morphine-6-glucuronide
- MPO:
-
Medial preoptic area
- αMSH:
-
Alpha-melanocyte stimulating hormone
- norBNI:
-
Nor-binaltorphimine
- PAG:
-
Periaqueductal gray
- PGE2 :
-
Prostaglandin E2
- RVM:
-
Rostral ventromedial medulla
- SRD:
-
Subnucleus reticularis dorsalis
- vlPAG:
-
Ventrolateral periaqueductal gray
Further Reading
Bingel U, Tracey I (2008) Imaging CNS modulation of pain in humans. Physiology (Bethesda) 23:371–380
Bodnar RJ, Kest B (2010) Sex differences in opioid analgesia, hyperalgesia, tolerance and withdrawal: central mechanisms of action and roles of gonadal hormones. Horm Behav 58:72–81
Fields HL, Basbaum AI (1978) Brainstem control of spinal pain-transmission neurons. Annu Rev Physiol 40:217–248, Classic paper that helped define the field
Heinricher MM, Fields HL (2012) Central nervous system mechanisms of pain modulation. In: McMahon S, Koltzenburg M (eds) Wall and Melzack's Textbook of Pain, 6th edn. Elsevier, London
Heinricher MM, Tavares I, Leith JL, Lumb BM (2009) Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 60:214–225
Le Bars D (2002) The whole body receptive field of dorsal horn multireceptive neurones. Brain Res Rev 40:29–44
Lovick TA (1997) The medullary raphe nuclei: a system for integration and gain control in autonomic and somatomotor responsiveness? Exp Physiol 82:31–41
Melzack R, Wall PD (1965) Pain mechanisms: a new theory. Science 150:971–979, Classic paper that helped define the field
Yaksh TL, Rudy TA (1978) Narcotic analgestics: CNS sites and mechanisms of action as revealed by intracerebral injection techniques. Pain 4:299–359, Classic paper that helped define the field
Yarnitsky D (2010) Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 23:611–615
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Bodnar, R., Heinricher, M.M. (2013). Central Mechanisms of Pain Suppression. In: Pfaff, D.W. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1997-6_102
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DOI: https://doi.org/10.1007/978-1-4614-1997-6_102
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-1996-9
Online ISBN: 978-1-4614-1997-6
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