Phantom limb pain

Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.

Chronic pain is an important public health problem that negatively impacts quality of life of affected individuals and exacts an enormous socio-economic cost. Currently available therapeutics provide inadequate management of pain in many patients. Acute pain states generally resolve in most patients. However, for reasons that are poorly understood, in some individuals, acute pain can transform to a chronic state. Our understanding of the risk factors that underlie the development of chronic pain is limited. Recent studies have suggested an important contribution of dysfunction in descending pain modulatory circuits to pain 'chronification'. Human studies provide insights into possible endogenous and exogenous factors that may promote the conversion of pain into a chronic condition. Descending pain modulatory systems have been studied and characterized in animal models. Human brain imaging techniques, deep brain stimulation and the mechanisms of action of drugs that are effective in the treatment of pain confirm the clinical relevance of top-down pain modulatory circuits. Growing evidence supports the concept that chronic pain is associated with a dysregulation in descending pain modulation. Disruption of the balance of descending modulatory circuits to favour facilitation may promote and maintain chronic pain. Recent findings suggest that diminished descending inhibition is likely to be an important element in determining whether pain may become chronic. This view is consistent with the clinical success of drugs that enhance spinal noradrenergic activity, such as serotonin/norepinephrine reuptake inhibitors (SNRIs), in the treatment of chronic pain states. Consistent with this concept, a robust descending inhibitory system may be normally engaged to protect against the development of chronic pain. Imaging studies show that higher cortical and subcortical centres that govern emotional, motivational and cognitive processes communicate directly with descending pain modulatory circuits providing a mechanistic basis to explain how exogenous factors can influence the expression of chronic pain in a susceptible individual. Preclinical studies coupled with clinical pharmacologic and neuroimaging investigations have advanced our understanding of brain circuits that modulate pain. Descending pain facilitatory and inhibitory circuits arising ultimately in the brainstem provide mechanisms that can be engaged to promote or protect against pain 'chronification'. These systems interact with higher centres, thus providing a means through which exogenous factors can influence the risk of pain chronification. A greater understanding of the role of descending pain modulation can lead to novel therapeutic directions aimed at normalizing aberrant processes that can lead to chronic pain.

A comparative effectiveness trial indicates that dorsal root ganglion stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to spinal cord stimulation.