Pain in the Context of Sensory Deafferentation.

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.

The pre-amputation pain and the postoperative deafferentation are the risk factors of phantom limb pain: a clinical survey in a sample of Chinese population.

BACKGROUND: To provide an overview of phantom limb pain (PLP) in China. This includes the prevalence of PLP and possible risk factors. METHODS: In a retrospective study, telephone interviews were conducted with 391 amputation patients who underwent extremity amputations at a tertiary hospital in China. RESULTS: PLP was found in 29% of the amputees. Pre-amputation pain (OR = 10.4, P = 0.002) and postoperative analgesia (OR = 4.9, P = 0.008) were identified as high-risk factors for PLP. 82.1% of PLP patients experienced pre-amputation pain. The average pain intensity of PLP was 5.1 ± 2.2, with 31.9% having severe intensity. The effects of PLP on the quality of the PLP patients were as follows: 7.8% of the patients had to limit their daily life and 29.0% of the patients had to limit their social activities. 17.3 and 25.7% of patients experienced depression and sleeping disorder respectively, while 18.9% had loss of interest and even 16.1% of PLP patients had attempted suicide. No effective treatments were found in 78.9% of these patients. CONCLUSIONS: PLP has markedly affected the lives of patients. Pre-amputation pain and postoperative epidural analgesia might be risk factors for the phantom limb pain after amputation. Prevention of pre-amputation pain and sudden post-amputation deafferentation should be recommended to the amputees.

Clinical Features of Pediatric Complex Regional Pain Syndrome: A 5-Year Retrospective Chart Review.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a painful condition of a limb characterized by a constellation of symptoms. Little is known about the clinical features of pediatric CRPS, with fewer than a dozen studies published to date. The aim of this study was to explore the clinical course of pediatric CRPS, with emphasis on clinical features and disease outcomes. A secondary aim was to discern differences in clinical features of pediatric CRPS with and without related movement disorders, and between children who had a favorable and unfavorable outcome. MATERIALS AND METHODS: We carried out a retrospective chart review of children with CRPS who presented to a pediatric Chronic Pain Clinic in Canada over a 5-year period (2012 to 2016). RESULTS: The study identified 59 children with CRPS (mean age: 12.7±2.5; 74.6% female; 72.9% lower extremity). In total, 87% (n=48) of children experienced complete resolution or significant improvement of CRPS, with a relapse rate of 15%. Overall, 25% (n=15) had a CRPS-related movement disorder. There were no differences in the clinical features of pediatric CRPS with or without related movement disorders. Children who experienced a favorable outcome had a significantly shorter symptom duration at the initial visit in comparison with children who experienced an unfavorable outcome. DISCUSSION: In this cohort, pediatric CRPS was most common in girls around the age of 12, usually in the lower extremity, and most experienced a favorable outcome. Further research is needed to better understand the prognosis and relapse rate of pediatric CRPS.

Reflex sympathetic dystrophy (causalgia) treatment with guanethidine.

Three cases of reflex sympathetic dystrophy (causalgia) were associated with cervical spondylosis. Two of them were related to sudden cervical trauma. Patients showed burning pain, hyperalgesia in a segmental distribution, and edema of the arms, hands, and fingers bilaterally. Oral administration of guanethidine sulfate was effective in all cases. Our results support the hypothesis that hypersensitivity to norepinephrine plays a role in reflex sympathetic dystrophy.

Horner syndrome with causalgia.

A previously healthy man presented with burning pain in the chest wall and arm; there was Horner syndrome on the same side. After extensive investigation, the disorder was attributed to a foraminal osteophyte involving the left T1 spinal root.

Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. Case report.

The authors describe the effectiveness of motor cortex stimulation (MCS) in a patient with complex regional pain syndrome (CRPS) Type II, formerly known as causalgia, with hemibody allodynia. During MCS, a subjective sensation of warm paresthesia developed in the painful hand and forearm and spread toward the trunk. Pain and allodynia in the areas associated with this sensation were alleviated significantly. The analgesic effect of stimulation proved to be long lasting and was still present at the 12-month follow up. The authors speculate that MCS might exert its effect through the modulation of thalamic activity in this particular case of CRPS with hemisensory deficit. A central mechanism associated with functional disturbance in noxious-event processing in the thalamus might have an important role in the pathogenesis of the condition.

Amenorrhea in a patient after treatment with gabapentin for complex regional pain syndrome type II.

A 35-year-old woman suffered a traumatic injury to her right sciatic nerve requiring nerve exploration and external neurolysis. Following the surgery, the patient developed complex regional pain syndrome (CRPS) type II and was treated with gabapentin for pain control. Three months after the initiation of gabapentin therapy (1800 mg/day), the patient reported complete cessation of her menses. Based on hormonal tests, her gynecologist concluded that her amenorrhea was secondary to gabapentin therapy. The patient was weaned off the gabapentin over 6 days with return of her menses 2 weeks later. I conclude that gabapentin has the potential to cause amenorrhea with return of menses occurring after discontinuation of the drug.

The rehabilitation of causalgia (complex regional pain syndrome-type II).

CRPS-type I or causalgia is a challenging pain syndrome and its pathogenesis remains controversial. Although its incidence is relatively low, the pain and suffering it causes can be severe and functionally debilitating. Early, accurate diagnosis permits initiation of appropriate therapeutic interventions and enhances the potential for successful treatment.

Unusual causes of arterial insufficiency.

Most patients with vascular insufficiency in the legs suffer from atherosclerosis. Thus, it is easy to miss the diagnosis in occasional patients with disease due to other causes. Mechanical and functional disorders which affect major arteries or arterioles are described.

Metallothionein deficiency in the injured peripheral nerves of complex regional pain syndrome as revealed by proteomics.

Complex regional pain syndrome (CRPS) is characterized by persistent and severe pain after trauma or surgery; however, its molecular mechanisms in the peripheral nervous system are poorly understood. Using proteomics, we investigated whether injured peripheral nerves of CRPS patients have altered protein profiles compared with control nerves. We obtained nerve samples from 3 patients with CRPS-2 who underwent resection of part of an injured peripheral nerve. Sural nerves from fresh cadavers with no history of trauma or neuropathic pain served as controls. Proteomic analysis showed that the number and functional distribution of proteins expressed in CRPS and control nerves was similar. Interestingly, metallothionein was absent in the injured nerves of CRPS-2, although it was readily detected in control nerves. Western blotting further confirmed the absence of metallothionein in CRPS-2 nerves, and immunohistochemistry corroborated the deficiency of metallothionein expression in injured nerves from 5 of 5 CRPS patients and 2 of 2 patients with painful neuromas. In contrast, all control nerves, including 5 sural nerves from fresh cadavers and 41 nerves obtained from surgically resected tumors, expressed MT. Furthermore, expression of S100 as a marker for Schwann cells, and neurofilament M as a marker of axons was comparable in both CRPS-2 and controls. Metallothioneins are zinc-binding proteins that are probably involved in protection against injury and subsequent regeneration after CNS damage. Their absence from the injured peripheral nerves of patients with CRPS-2 suggests a potential pathogenic role in generating pain in the damaged peripheral nerves.

Causalgic form of postphlebitic syndrome. A variety of reflex sympathetic dystrophy caused by acute deep thrombophlebitis.

The causalgic form of the postphlebitic syndrome or reflex sympathetic dystrophy resulting from acute deep thrombophlebitis is a relatively uncommon and, unfortunately, frequently unrecognized form of the postphlebitic syndrome. The usual signs of venous insufficiency are minimal, but severe burning pain is characteristic, usually increased by dependency. The diagnosis is confirmed by phlebography and the response to a lumbar sympathetic block. A lumbar sympathectomy produces permanent pain relief.

The causalgia-dystonia syndrome.

We report 18 patients (16 women and two men) with causalgia and dystonia, triggered by peripheral injuries in 15 cases and occurring spontaneously in three. The injury was often trivial, and did not cause overt peripheral nerve lesions. The mean age at presentation was 28.5 years. None had a family history of dystonia. The leg was affected initially in 12 patients, the arm in the remaining six cases. All had burning pain, allodynia and hyperpathia, along with vasomotor, sudomotor and trophic changes. All developed dystonic muscle spasms in the affected part. Dystonia always appeared at the same time or after the causalgia. The spasms were typically sustained, producing a 'fixed' dystonic posture, in contrast to the mobile spasms characteristics of idiopathic torsion dystonia. There was spread of the causalgia and of the dystonia from its initial site both in the affected limb and to other extremities, the latter in hemiplegic, transverse and triplegic distribution. All investigations were normal. All modes of conventional treatment failed to relieve either the pain or the dystonia, but two patients recovered spontaneously. At present it is impossible to decide whether this distressing syndrome is a true functional disorder of the central nervous system, or is of psychogenic origin.

Causalgia and reflex sympathetic dystrophy: does the sympathetic nervous system contribute to the generation of pain?

The striking response of causalgia and reflex sympathetic dystrophy (RSD) to sympatholytic procedures together with signs of autonomic nervous system abnormalities suggest that the sympathetic efferent system can generate or enhance pain (sympathetically maintained pain, SMP). This concept is supported by human and animal experiments indicating that sympathetic activity and catecholamines can activate primary afferent nociceptors. Some clinical evidence, however, calls the SMP concept into question and alternative explanations have been advanced. In this review, we describe the clinical features of causalgia and RSD and the evidence for sympatholytic efficacy. The major barrier to proving the SMP concept is that all available sympatholytic procedures are problematic. We conclude that, although the weight of current evidence supports the SMP concept and its relevance to causalgia and RSD, it remains unproven by scientific criteria. More careful adherence to diagnostic criteria and well-controlled trials of sympatholysis are needed to finally settle the issue.