Trends in Neurosciences
Volume 25, Issue 6, 1 June 2002, Pages 319-325
Journal home page for Trends in Neurosciences

Review
Chronic pain and medullary descending facilitation

https://doi.org/10.1016/S0166-2236(02)02157-4Get rights and content

Abstract

Chronic pain, whether the result of nerve trauma or persistent inflammation, is a debilitating condition that exerts a high social cost in terms of productivity, economic impact and quality of life. Currently available therapies yield limited success in treating such pain, suggesting the need for new insight into underlying mechanism(s). Here, we examine the likelihood that sustained activation of descending modulatory pathways that facilitate pain transmission could underlie some states of chronic pain. Such activation of descending facilitatory pathways might be the result of neuroplastic changes that occur at medullary sites in response to persistent input of pain signals. Understanding the mechanisms of descending facilitation and the spinal effects of such discharge could provide new insights into the modulation of chronic pain.

Section snippets

Descending facilitation of spinal nociceptive input

Perhaps because it is difficult to envisage the physiological advantages of a pronociceptive system, acceptance of the existence and potential importance of descending facilitatory influences has been slow to develop. Electrical and/or chemical stimulation of sites outside the RVM (e.g. of dorsal reticular [21] or pretectal [22] nuclei) can also enhance behavioral and spinal neuronal responses to peripheral noxious stimulation. However, the RVM has been studied most extensively and is likely to

RVM cells and descending facilitation

Much of what we currently understand about the RVM in relation to processing and modulation of pain is based on the characterizations by Fields and colleagues of three types of neurons found in the RVM. Based on response characteristics to noxious thermal stimulation of the tail, these cells have been described as ‘ON’, ‘OFF’ and ‘neutral’ 15., 39., 40.. OFF-cells are tonically active and pause in firing immediately before tail (or hind limb) withdrawal from a noxious thermal stimulus. ON-cells

Supraspinal modulation of chronic pain

Anatomical and pharmacological criteria suggest that facilitatory and inhibitory pathways are distinct, and are likely to be activated simultaneously in conditions of acute nociception. Thus, a ‘balance’ between these systems could be struck. However, in conditions of persistent nociceptive input, neuroplastic changes might occur in the RVM and elsewhere to yield a sustained facilitatory influence that drives exaggerated pain. Strong evidence supports the idea that manifestations of chronic

Facilitation of painful inputs and neuropathic pain

Converging evidence suggests that some abnormal pain states depend on descending facilitatory drive from the RVM. Persistent noxious input produced by injection of formalin into the hind paw or application of mustard oil to the hind-limb skin facilitates the nocifensive tail-flick reflex 59., 60., 61.. Such facilitation of acute pain appears to be mediated through the RVM 59., 60., specifically by activation of an NMDA-receptor-mediated mechanism 61., 62.. The behavioral signs of neuropathic

Facilitation of painful inputs and inflammatory pain

Similar experimental strategies to those already described for neuropathic pain effectively block the hyperalgesia that follows peripheral inflammation. Spinal transection or injections of lidocaine into the RVM reverse behavioral and electrophysiological signs of facilitated nociception in rats with carrageenan-induced inflammation of the hind paw 52., 72., 73.. Complete Freund's adjuvant (CFA) produces behavioral hyperalgesia and increases expression of Fos-like immunoreactivity (Fos-LI),

Concluding remarks

Our understanding of nociceptive circuits, especially those that actually promote pain, is still in its infancy. Pain has important physiological functions, warning us of actual or impending tissue damage. Less obvious is the physiological importance of mechanisms for pain facilitation. In the case of persistent injury, it is easy to postulate that these mechanisms exist to protect the injured region by forcing guarding behavior and restricting the use of the injured site. Neuropathic pain,

Acknowledgements

We thank Herbert Proudfit for assistance with Fig. 3.

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