Phantom limb pain and pain interference in adults with lower extremity amputation: The moderating effects of age.

Purpose/Objective: To determine whether the relationship between phantom limb pain severity and pain-related interference was moderated by age and to compare 2 theoretical perspectives used in the literature to account for age-related differences in the experience of chronic pain. Research Method/Design: Analysis of survey data provided by 375 adults with lower extremity amputations who reported phantom limb pain. Results: The relationship between phantom limb pain severity and pain-related interference was shown to be moderated by age (β = -.10, p     

The prevalence of phantom limb experience in amputees.

Reviewed the records of 716 amputees who utilized Canadian prosthetic facilities to determine the prevalence of phantom limb pain or sensation and the possible influence of demographic variables on their presence. The prevalence of phantom pain (62.4%) and phantom sensation (84.1%) tended to confirm recent surveys in other nationalities. Years since amputation was the only variable found to influence the report of either pain or sensation. Ss who lost their limbs prior to 1960 reported significantly more pain (73.3%) than Ss who lost their limbs after 1976 (51.1%). There was also a slight tendency for older Ss to report phantom limb pain more often than younger Ss. Findings suggest that the incidence of phantom limb pain is declining. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Healthy youth development as a model for youth health promotion. A review

To explore the possible mechanisms of phantom limb discomfort after amputation, three amputees with phantom limb pain were studied. This study examined the change of regional cerebral blood flow using technetium-99m hexamethylpropyleneamine oxime-single photon emission computerized tomography, which was arranged at the time of severe phantom limb discomfort and after the discomfort subsided or was completely relieved. Nine representative transverse slices parallel to the orbitomeatal line were selected for quantification. The cortical ribbon (2-cm thickness) was equally subdivided into 12 symmetrical pairs of sector regions of interest in each slice. The irregularly shaped regions of interest were drawn manually around the right thalamus and basal ganglion and then mirrored to the left thalamus and basal ganglion. The contralateral to ipsilateral ratio of regional cerebral blood flow for each area was calculated. The intensity of phantom limb pain was evaluated on a 0 to 10 visual analog scale. In Cases 1 and 2, the contralateral to ipsilateral regional cerebral blood flow ratios of multiple areas of the frontal, temporal, or parietal lobes were increased at the time of more severe phantom limb pain, and the ratios were normalized or even decreased when the phantom limb pain subsided. In Case 3, increased contralateral to ipsilateral regional cerebral blood flow ratios were also found over the frontal, temporal, and parietal lobe. However, most of the increased regional cerebral blood flow ratios of regions of interest in the first study persisted in the follow-up study. Also, the regional cerebral blood flow ratios of greater number of regions of interest of the same gyrus and new gyrus were increased. There was no significant right-left difference of regional cerebral blood flow over bilateral thalami and basal ganglia in all three cases. The results suggested that phantom limb pain might be associated with cortical activation involving the frontal, temporal, or parietal cortex, and it may imply the possibility of the existence of an ascending polysynaptic pathway that conveys the uncomfortable phantom limb sensation to the cerebral cortex. These findings may also indicate that reorganization of the cortical blood flow occurs in amputees. However, it is still difficult to conclude that the changes in regional cerebral blood flow were attributable directly to pain. With no comparison group of amputees and because of the small number of cases, it is hard to generalize about cerebrocortical involvement in phantom pain, and it is possible that the findings represent a normal phenomenon seen after 'amputation. Another possibility is that the findings represent increased arousal caused by pain rather than an intrinsic pain pathway. Further study is worthwhile.     

The cortical somatotopic map and phantom phenomena in subjects with congenital limb atrophy and traumatic amputees with phantom limb pain

The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.     

Phantom sensations generated by thalamic microstimulation

Many amputees have a sense of their missing 'phantom' limb. Amputation can alter the representation of the body's surface in the cerebral cortex and thalamus, but it is unclear how these changes relate to such phantom sensations. One possibility is that, in amputees who experience phantom sensations, the region of the thalamus that originally represented the missing limb remains functional and can give rise to phantom sensations even when some thalamic 'limb' neurons begin to respond to stimulation of other body regions. Here we use microelectrode recording and microstimulation during functional stereotactic mapping of the ventrocaudal thalamus in amputees to determine both the responses of the neurons to stimulation of the skin and the perceptual effects of electrical activation of these neurons. Thalamic mapping revealed an unusually large thalamic stump representation, consistent with the findings from animal experiments. We also found that thalamic stimulation in amputees with a phantom limb could evoke phantom sensations, including pain, even in regions containing neurons responsive to tactile stimulation of the stump. These findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms.     

Pain from excitation of identified muscle nociceptors in humans

The technique of intraneural microstimulation (INMS) combined with microneurography was used to excite and to record impulse activity in identified afferent peroneal nerve fibers from skeletal muscle of human volunteers. Microelectrode position was minutely adjusted within the impaled nerve fascicle until a reproducible sensation of deep pain projected to the limb was obtained during INMS. During INMS trains of 5-10 s in duration and at threshold for sensation, volunteers perceived a well defined area of deep pain projected to muscle. Psychophysical judgements of the magnitude of pain increased with increasing rates of INMS between 5 and 25 Hz. Also, the area of the painful projected field (PF) evoked during trains of INMS of various duration but constant intensity and rate typically expanded with duration of INMS. The intraneural microelectrode was alternatively used to record neural activity originating from primary muscle afferents. Eight slowly adapting units with moderate to high mechanical threshold were identified by applying pressure within or adjacent to the painful PF. Conduction velocities ranged from 0.9 to 6.0 m/s, and fibers were classed as Group III or Group IV. Capsaicin (0.01%) injected into the RF of two slowly conducting muscle afferents (one Group III and one Group IV) produced spontaneous discharge of each fiber and caused intense cramping pain, suggesting that the units recorded were nociceptive. Our results endorse the concept that the primary sensory apparatus that encodes the sensation of cramping muscle pain in humans is served by mechanical nociceptors with slowly conducting nerve fibers. Results also reveal that muscle pain can be precisely localized, although the human cortical function of locognosia for muscle pain becomes blunted as a function of duration of the stimulus.     

Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms

This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P < 0.01) over painful sites and a tendency to increased sensitivity to non-painful cold (P < 0.06) at all sites compared to controls, but there was no difference between groups regarding tactile perception thresholds. Compared to controls, patients demonstrated increased sensitivity to pressure pain (P < 0.001), cold pain (P < 0.001) and heat pain (P < 0.02) over all tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P < 0.003). Intragroup comparisons showed that patients had increased sensitivity to pressure pain (P < 0.01) and light touch (P < 0.05) in the site of maximal pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.     

Postherpetic neuralgia: irritable nociceptors and deafferentation

Postherpetic neuralgia (PHN) is a common and often devastatingly painful condition. It is also one of the most extensively investigated of the neuropathic pains. Patients with PHN have been studied using quantitative testing of primary afferent function, skin biopsies, and controlled treatment trials. Together with insights drawn from an extensive and growing literature on experimental models of neuropathic pain these patient studies have provided a preliminary glimpse of the pain-generating mechanisms in PHN. It is clear that both peripheral and central pathophysiological mechanisms contribute to PHN pain. Some PHN patients have abnormal sensitization of unmyelinated cutaneous nociceptors (irritable nociceptors). Such patients characteristically have minimal sensory loss. Other patients have pain associated with small fiber deafferentation. In such patients pain and temperature sensation are profoundly impaired but light moving mechanical stimuli can often produce severe pain (allodynia). In these patients, allodynia may be due to the formation of new connections between nonnociceptive large diameter primary afferents and central pain transmission neurons. Other deafferentation patients have severe spontaneous pain without hyperalgesia or allodynia and presumably have lost both large and small diameter fibers. In this group the pain is likely due to increased spontaneous activity in deafferented central neurons and/or reorganization of central connections. These three types of mechanism may coexist in individual patients and each offers the possibility for developing new therapeutic interventions.     

Noise-driven neuroplasticity in self-organizing feature maps: a neurocomputational model of phantom limbs

The term "phantom limb" denotes the sensation that an extremity is present although it has been lost. A number of clinical features and recent findings of cortical map plasticity after destruction of afferent pathways (deafferentation) suggest that phantom limbs are caused by large-scale cortical reorganization processes. However, in paraplegics, who also suffer from cortical deafferentation, phantom sensations rarely develop, and if they do, they are weak, lacking in detail, and delayed, occurring after months. This has been taken to suggest a non-cortical genesis of phantom limbs. This article proposes a biologically plausible minimal neural network model to solve this apparent puzzle. Deafferentation was simulated in trained self-organizing feature maps. Reorganization was found to be directed by input noise. According to the model, the production of input noise by the deafferented primary sensory neuron promotes cortical reorganization in amputees. No such noise is generated or conducted to the cortex in paraplegics.     

Effects of tap withdrawal response habituation on other withdrawal behaviors: The localization of habituation in the nematode Caenorhabditis elegans.

Four experiments were conducted to identify the possible loci of habituation of the nematode tap withdrawal response (TWR) by charactering the effects of TWR habituation on other nonmechanosensory withdrawal behaviors that are mediated by overlapping sets of neurons. Experiments 1–2 established behavioral and anatomical relationships between spontaneous and tap-induced backward locomotion in the worm. Experiment 3 demonstrated that habituation of the TWR affected neither the magnitude nor frequency of spontaneous reversal activity. Experiment 4 extended this result to an evoked response: Habituation of the TWR had no effect on reversals evoked by a thermal stimulus. These studies, which show that the loci of change associated with habituation of the TWR are presynaptic to the interneurons and motor neurons that control locomotion, probably distributed among the mechanosensory neurons, illustrate that a complete understanding of plasticity requires a knowledge of both the anatomical and molecular substrates of change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Current principles of multidisciplinary treatment of pain in orthopedic clinics

Differentiated strategy of treating patients with acute and chronic pain is developed. Preemptive analgesia is a priority trend in the treatment of acute postoperative pain. The most prevalent method of postoperative analgesia is prolonged opioid epidural analgesia carried out in intensive care wards and other wards by an acute pain management team. For treating patients with chronic painful syndromes, protocols of initial clinical and diagnostic evaluation are developed, permitting the choice of individual treatment strategy. Differentiated complex drug therapy planned with consideration for individual course of the painful syndrome is the basis of treating patients with phantom pain syndrome. Algorithms of differentiated therapy of radicular and spondylogenic pain are designed. Stage-by-stage analysis of treatment efficacy is carried out using modern electrophysiological methods. Realization of the proposed organization principles improved the efficacy of postoperative analgesia to 88.2%, prevented the development of postoperative painful syndrome in 35.6% cases, decreased the incidence of phantom pain syndrome after amputation of the limb from 63.3 to 31.6% and increased the efficacy of this syndrome treatment to 70.1%, and increased the efficacy of treating vertebrogenic painful syndromes to 82.3%.     

{l}-DOPA-induced air-stepping in the preweanling rat: Electromyographic and kinematic analyses.

Ontogenetic changes in intralimb coordination may result from maturation of the central pattern for locomotion. maturation of peripheral efferents, changes in afferent modulation of the centrally generated pattern, interactions with the substrate, biomechanical changes within the limb itself, or a combination of these. Electromyograms obtained from three hindlimb extensors of rats on Postnatal Days (PND) 5, 10, 15, or 20, during episodes of coordinated {l}-DOPA-induced air-stepping, showed that muscle activation preceded extension of the corresponding joints at all ages. The delay between the onset of extensor activity and the onset of joint extension increased during ontogeny and was greatest at PND 20. Ontogenetic changes in the relative timing of muscle activity and corresponding joint movements probably resulted from changes in biomechanical factors, changes in afferent modulation of central motor output, or both. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pain management from the viewpoint of the anesthetist

In a pain clinic team the anesthetist has the knowledge and experience concerning the peripheral and central neural blockades. The value of the diagnostic, prognostic and therapeutic blockades is today under discussion. Patients with a chronic regional pain syndrome (CRPS) can find some relief with a series of somatic and sympatholytic blockades, which allow an aggressive physiotherapy. Epidural steroid injections are helpful in radiculopathic pain. In other types of pain (neuropathic, postherpetic, failed back surgery syndrome, abdominal, cervico-cephalgic, phantom limb pain und tumor pain) the spinal cord stimulation (SCS) and the intrathecal morphine pump are approved methods for intactable pain.     

Epiduritis after long-term pain therapy with an epidural catheter--review of the literature with a current case report

Patients suffering from vascular disease are often a challenge for the acute pain service. Ischaemia, impaired wound healing, stump and phantom limb pain often require a complex analgesic regimen. Invasive measures such as spinal or epidural catheters can be very helpful but carry the risk of infection, as shown by this case report. A 53-year-old woman with a ten-year history of diabetes developed arterial vascular disease. Her right lower leg had been amputated two years previously. She was now admitted with necroses of the left forefoot. A bypass operation was performed under general anaesthesia. Because of intractable ischaemic pain, she was provided with an epidural catheter by the acute pain service. The bypass occluded, however, and a few days later her left lower leg also had to be amputated, this operation being performed under epidural anaesthesia with bupivacaine. The catheter was subsequently used for postoperative pain control and as a means to prevent phantom limb pain. When signs of superficial catheter infection were noticed days later, the catheter was immediately removed. Intractable pain then developed in the left leg which could not be sufficiently controlled with opioids and NSAIDs, and so a second epidural catheter was inserted one segment rostrally. Several days later the infected vascular prosthesis had to be removed followed by amputation of the thigh, this operation also being performed in epidural anaesthesia. Eleven days after insertion of the first epidural catheter, the patient complained of low back pain and headache. Examination by a neurologist revealed no signs of intraspinal infection. The second epidural catheter dislocated at this point in time and it was decided to introduce a third one, this being the only means to treat the otherwise intractable stump pain. Ten days later meningism, Kernig's sign and leucocytosis developed. NMR tomography detected intraspinal fluid in the epidural space at the dorsal border of the spinal canal. A hemilaminectomy was performed. The spinal epidural space showed signs of inflammation of the adipose tissue, but no pus. A little necrotic material and residues of an old haematoma were removed and the epidural space was lavaged. Specimens taken from the epidural material revealed colonisation with staphylococcus epidermidis, which was sensitive to the broad spectrum antibiotics formerly given to the patient to treat the infection in the left stump. By the next day, all signs of epiduritis had disappeared and the patient recovered completely.     

Vincristine disturbs spontaneous firing of the afferent nerve fibre in ampullary electroreceptor organs

Ampullary electroreceptor organs of the catfish were apically exposed to 0.3 mM vincristine in order to investigate the part played by the microtubular system in stimulus transduction. The main effects were repetitive firing of the afferent fibre, a reduction of the mean spontaneous activity and a reduction of the spike amplitude two to four days after exposure to vincristine. The mean sensitivity was less susceptible to vincristine than the spontaneous activity. Since the shape of the frequency curves remained unchanged and similar effects as described above were also observed after denervation, we conclude that vincristine most likely does not affect electroreceptor cell functioning, but causes degeneration of the afferent fibre.     

Glycine-glutamate interactions at the NMDA receptor: role of cysteine residues

The term "centrocentral anastomosis" is used to describe the end-to-end connection across interposed nerve grafts between paired fascicular groups of the proximal stump of a severed nerve. In 22 patients harboring a painful terminal neuroma following amputation of a lower limb (20 neuromas on the sciatic nerve and two on the peroneal nerve), a centrocentral anastomosis was performed on the end of the sectioned nerve to treat pain that had not improved with conventional conservative treatment. Follow-up review at 1 year revealed that the typical neuroma pain had disappeared in all cases, although sporadic diffuse pain persisted in four. Where previous phantom sensation was present, no change was observed. The results presented here are consistent with laboratory findings demonstrating the absence of neuroma formation after centrocentral anastomosis. Therefore, this technique is recommended for the treatment of painful amputation neuroma.     

Evidence for altered cell-mediated immunity in postmastectomy lymphoedema

Patients with chronic lymphoedema are prone to develop chronic infections and various tumours in the lymphoedematous limb, suggesting that regional immune surveillance is impaired. To test the hypothesis that cutaneous cell-mediated immunity is impaired, 35 women with postmastectomy lymphoedema were investigated using dinitrochlorobenzene to test the afferent and efferent loops of the allergic contact immune response. The results support the role of lymphatics as an important component of the immune response to allergens by the demonstration of impairment of both the afferent and efferent loops of the allergic contact dermatitis reaction, and confirm that there is suppression of immune competence in a lymphoedematous limb.     

Phantom limb experience in children and adults: Cognitive and affective contributions.

Reviews the literature on cognitive and affective processes that contribute to phantom limb (PL) experience in children and adults and challenges the view that psychologically or emotionally induced sensations or pain referred to the PL necessarily represent a psychopathological response to amputation. It is argued that thoughts and feelings may trigger sensations referred to the PL in psychologically healthy individuals and that the painful or painless PL is not a symptom of a psychological disorder. A model is presented that involves a sympathetic-efferent somatic-afferent cycle of activity initiated by higher brain centers involved in cognitive and affective processes to explain psychologically and emotionally triggered PL sensations. The experience of a PL is determined by a complex interaction of inputs from the periphery and widespread regions of the brain subserving sensory, affective and cognitive processes. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)