Chronic pain encompasses a spectrum of clinical scenarios involving both peripheral and central pain syndromes. In this article, the author discusses the progression of understanding about the pathophysiology of pain, culminating in the gait theory hypothesis. The author addresses pain from peripheral nerve injury, spinal cord injury, and brain injury and stroke and discusses the basic science behind the rationale for current management schemes and pain treatments (both pharmacological and surgical). The author concludes by summarizing the success (or lack thereof) of surgical treatment modalities for chronic pain. In this update, the author updates the section on cordotomy for chronic pain, focusing on recent and upcoming trials.
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• Both physical and psychological aspects of chronic pain are significant and should be considered.
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• Treatment of chronic pain is multidisciplinary with simultaneous pharmacological, behavioral, exercise, and procedural treatments often needed in concert.
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• Surgical strategies have been devised to downregulate pain receptors peripherally and pain pathways centrally.
Historical note and terminology
Much of the modern approach to treatment of pain began in the early 19th century with advances in the understanding of spinal cord and nerve root anatomy. In 1809, Walker proposed the idea that spinal roots were functionally divided into anterior motor roots and posterior sensory roots (116). In 1911, Charles Bell, a Scottish anatomist and neurosurgeon, furthered this concept when he circulated a pamphlet describing the motor role of the anterior or ventral nerve root of the spinal cord (06). In 1822, the French physiologist François Magendie showed that dorsal roots were specifically associated with sensation, confirming Bell's conclusions about the anterior nerve root (65). It was not until the early 1900s, however, that Spiller first described the spinal pain pathways as they are understood today (102). Central pain syndromes were also described, notably by Marchet in 1811, associating pain with what would later be recognized as Wallenberg syndrome (66).
As the anatomy of pain became understood, attempts at surgical treatments for pain also advanced. Létiébant, Dana, Bennet, and Abbe were the pioneers of ablative rhizotomies in the treatment of both peripheral and cranial nerve pain syndromes.
Trigeminal neuralgia, which had been described in literary documents for over 200 years, was first surgically treated by Hartley in 1891; this was done using the extradural temporal approach to section the nerve (34). Continuing with the ablative approach to treatment, surgeons such as Dandy, Gardner, and Miklos noted the compression of the trigeminal nerve by vascular loops. Nonetheless, rhizotomy treatments remained the first line of surgical therapy until 1967, when Jannetta innovated the procedure of microvascular decompression (47).
Advancing the understanding of the anatomy of the anterolateral system was taking place at the same time. Bell, through unmagnified dissections, and Schiff and Brown-Séquard, using experimental techniques, attempted to map the sensory pathways through the spinal cord and cerebrum. Advances were made in the late 1800s by patient observation coupled with postmortem examination. Müller and Gowers independently reported on 2 separate cases involving spinal cord trauma that greatly advanced the understanding of pain fiber location in the spinal cord (71; 30). In 1905, Spiller described a patient with loss of pain and temperature sensation in the lower extremities. Autopsy revealed the patient had bilateral tuberculomas involving the lower thoracic anterolateral tracts (102). In 1911, with the encouragement of Spiller, Martin pioneered the cordotomy procedure in a human subject. The results were encouraging, and a new technique was born (103).
Another phase in the management of chronic pain developed as a result of interest in the endocrine system as a modulator of cancer. Management of metastatic carcinoma once involved surgical ablation of endocrine tissue based on observations of Huggins and others on tumor regression with orchiectomy, adrenalectomy, and pituitary ablation (45; 44; 91). In 1953, Luft and colleagues reported marked improvement of pain with pituitary ablation in some patients with prostate cancer (63). Similar anecdotal reports fueled interest in pituitary ablation as a treatment for chronic pain.
The discovery that cordotomies and spinothalamic tractotomies did not effectively provide long-term relief for shoulder, neck, and facial pain led to the use of stereotaxy in the field of neurosurgery. Spiegel and Wycis were the first to perform stereotactic lesioning of the mesencephalon and thalamus (101). Hitchcock later used the technique to lesion the pons and trigeminal spinothalamic pathways. This provided good results in the treatment of head and neck pain with increased accuracy. It also provided insights into the pathophysiology of chronic denervation pain (40; 41).
Melzack and Wall’s gate theory, published in 1965, led to a landmark advance in the management of pain. The concept that afferent painful stimuli may be modulated by a gating mechanism involving the spinal cord led to the introduction of neuromodulation (70). In 1965, Sweet implanted a peripheral nerve stimulator, the first augmentation procedure for the treatment of pain (106). In the following years, Shealy performed the first dorsal column stimulator (94). Mazars showed that stimulation of the posteroventral lateral thalamic nucleus was effective in treating chronic pain (67). Richardson and Akil implanted the first periaqueductal gray stimulator in humans (84; 85). Tsubokawa has reported the efficacy of motor cortex stimulation in thalamic deafferentation pain (109).
Many ablative techniques, thus, were replaced by augmentative techniques due to the gate theory. One notable exception to this is found in the treatment of brachial plexus ablation pain due to deafferentation. In 1972, Sindou introduced the use of dorsal root entry zone ablation; this has since been modified to use radiofrequency thermocoagulation to cause the lesioning (98).
The opium poppy has been recognized for centuries as a source of analgesia with morphine, first extracted and described in 1806.
The discovery of morphine receptors in the central nervous system and spinal cord in the early to mid-1970s led to their use in the treatment of central pain syndromes. This has become a cornerstone in the adjunctive treatment of pain and has also led to the use of other medications through intrathecal pump technology.
Nomenclature. The quality and characteristics of chronic pain will differ appreciably based on the pathophysiological substrate as well as the emotional component of the experience of pain. Definitions of painful syndromes signify the often subtle differences between these descriptions. Allodynia refers to increased pain with light tactile stimulation. Hyperalgesia refers to a magnified pain response to noxious stimuli. Hyperesthesia refers to increased sensitivity to tactile stimulations. For example, postherpetic neuralgia is characterized either by a constant burning deep tissue pain or an episodic pain described as lancinating (118). Peripheral nerve pain from injuries or entrapment can be constant or intermittent as well. Pain with nerve injury or entrapment can radiate in a retrograde or anterograde fashion along the course of the nerve. Central pain after spinal cord injury can occur as constant burning pain associated with painful paresthesias or intermittent stabbing pain (97). Phantom pain, defined as an unpleasant nociception in an absent limb can occur in up to 85% of amputees (117). Other well-described pain syndromes can involve joints, the pelvis or perineum in either sex, the coccyx and rectum, and the ribcage. Central pain syndrome encompasses the entire syndrome of pain perception and can involve abnormalities in temperature sensitivity or pain brought about by active or passive joint movement (kinesthetic allodynia) (29).
One area of confusion is the terminology for chronic nerve pain and injury. Boas refers to Type I complex regional pain syndrome as analogous to reflex sympathetic dystrophy pertaining to pain “without pathophysiological connotations.” Type II complex regional pain syndrome mirrors causalgia as being incited by a discrete injury or insult (08).