J Pain. 2013 Jul 19.
Shin NY, Kang DH, Jang JH, Park SY, Hwang JY, Kim SN, Byun MS, Park HY, Kim YC.
Multiple brain areas involved in nociceptive, autonomic, and social-emotional processing are disproportionally changed in patients with complex regional pain syndrome (CRPS). Little empirical evidence is available involving social cognitive functioning in patients with chronic pain conditions. We investigated the ability of patients with CRPS to recognize the mental/emotional states of other people. Forty-three patients with CRPS and 30 healthy controls performed the Reading Mind in the Eyes Test, which consists of photos in which human eyes express various emotional and mental states. Neuropsychological tests, including the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time test, were administered to evaluate other cognitive functions. Patients with CRPS were significantly less accurate at recognizing emotional states in other persons, but not on other cognitive tests, compared with control subjects. We found a significant association between the deficit in social-emotion recognition and the affective dimension of pain, whereas this deficit was not related to the sensory dimension of pain. Our findings suggest a disrupted ability to recognize others’ mental/emotional states in patients with CRPS.
This article demonstrated a deficit in inferring mental/emotional states of others in patients with CRPS that was related to pain affect. Our study suggests that additional interventions directed toward reducing distressful affective pain may be helpful to restore social cognitive processing in patients with CRPS.
RS – addressing all the dimensions of pain is vital in a comprehensive treatment & training programme: physical, emotional & cognitive. Awareness of deficits such as ‘inferring mental/emotional states of others’, as seen in this study, allows clinicians to account for certain behaviours and responses that can be seen during the assessment process and treatment sessions. Subsequently, the therapy choice can be made on an individual basis to target the deficits.
Altered Resting-State Functional Connectivity in Complex Regional Pain Syndrome.
J Pain. 2013 Jun 18.
Bolwerk A, Seifert F, Maihöfner C.
This study explored the functional connectivity between brain regions implicated in the default mode network, the sensorimotor cortex (S1/M1), and the intraparietal sulcus (IPS/MIP) at rest in patients with complex regional pain syndrome. It also investigated how possible alterations are associated with neuropathic pain. Our group used functional magnetic resonance imaging to investigate functional brain connectivity in 12 complex regional pain syndrome patients in comparison with that in 12 age- and sex-matched healthy controls. Data were analyzed using a seed voxel correlation analysis and an independent component analysis. An analysis of covariance was employed to relate alterations in functional connectivity with clinical symptoms. We found significantly greater reductions in functional default mode network connectivity in patients compared to controls. The functional connectivity maps of S1/M1 and IPS/MIP in patients revealed greater and more diffuse connectivity with other brain regions, mainly with the cingulate cortex, precuneus, thalamus, and prefrontal cortex. In contrast, controls showed greater intraregional connectivity within S1/M1 and IPS/MIP. Furthermore, there was a trend for correlation between alterations in functional connectivity and intensity of neuropathic pain. In our findings, patients with complex regional pain syndrome have substantial spatial alterations in the functional connectivity between brain regions implicated in the resting-state default mode network, S1/M1, and IPS/MIP; these alterations show a trend of correlation with neuropathic pain intensity.
This article presents spatial alterations in the functional resting-state connectivity of complex regional pain syndrome patients. Our results add further insight into the disease states of CRPS and into the functional architecture of the resting state brains of pain patients in general.
RS: Pain emerges from the body. That is where we feel it undoubtedly. It can be a difficult leap to understand that the neural correlate sits within the brain. There is no pain centre but rather a widespread group of neurons in different brain regions that when activated, create a neurotag or neurosignature that manifests as pain where the brain perceives a threat that requires protection. It is no surprise therefore, to see a further study highlight altered activity within the brain in CRPS patients compared to a control group. From a clinical perspective, it demonstrates that we have to ‘think brain’ within the reasoning behind the design of a rehabilitation programme and in appropriate cases use therapies such as graded motor imagery
A Disturbance in Sensory Processing on the Affected Side of the Body Increases Limb Pain in Complex Regional Pain Syndrome.
Clin J Pain. 2013 Jun 19.
Drummond PD, Finch PM.
The aim of this study was to determine whether a central disturbance in somatosensory processing contributes to limb pain in complex regional pain syndrome (CRPS).
In 37 patients with CRPS, the effect of cooling the ipsilateral forehead on pain in the affected limb was compared with the effect of cooling the contralateral forehead. In addition, symptoms associated with cold-evoked limb pain were explored.
Limb pain generally increased when the ipsilateral side of the forehead was cooled but did not change when the contralateral side of the forehead was cooled. Increases were greatest in patients with heightened sensitivity to cold, brushing, and pressure-pain in the ipsilateral forehead, in patients with heightened sensitivity to pressure-pain in the limbs, and in patients with chronic symptoms. In contrast, sensitivity to light touch was diminished in the CRPS-affected limb of patients whose limb pain remained unchanged or decreased during ipsilateral forehead cooling.
These preliminary findings suggest that a central disturbance in sensory processing and pain modulation, which extends beyond the affected limb to the ipsilateral forehead, contributes to symptoms in a subgroup of patients with CRPS.
RS: A number of patients who present with pain that is underpinned by a component of central sensitisation will also, being given the chance, describe pain in other body regions and body systems. Being vigilant to this possibility is fundamental to a complete assessment, the conclusions of which will guide the treatment programme.
Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6months.
Pain. 2013 Jun 27.
Lenz M, Uçeyler N, Frettlöh J, Höffken O, Krumova EK, Lissek S, Reinersmann A, Sommer C, Stude P, Waaga-Gasser AM, Tegenthoff M, Maier C.
There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1year) and after 6months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β). We found bilaterally increased proinflammatory TNF-α and MIP-1β and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.
RS: ‘Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS’. In some patients there is an inflammatory profile that should be noted and treated as early as possible. On-going inflammation will cause a persisting bombardment of danger signals to the spinal cord and to the higher centres. The brain does want to know about inflammation and when detected it typically hurts, the purpose being that we need to know (consciously) so that we take appropriate action. Tackling inflammation early may have a beneficial effect upon this process.
Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses.
Pain. 2013 Jul 22.
Lorimer Moseley G, Gallace A, Di Pietro F, Spence C, Iannetti GD.
In unilateral upper limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located, relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In two separate cross-sectional randomized experiments, ten (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after nine-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Δ°C =0.47 ± 0.14°C), but not if prism glasses made the hand appear to be on the body midline (Δ°C =0.07 ± 0.06°C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Δ°C =0.28 ± 0.14°C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C = -0.30 ± 0.15°C). Friedman’s ANOVA and Wilcoxon’s pairs tests upheld the results (p <0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.
And, another paper here:
Spatially defined modulation of skin temperature and hand ownership of both hands in patients with unilateral complex regional pain syndrome.
Brain. 2012 Dec;135(Pt 12):3676-86.
Moseley GL, Gallace A, Iannetti GD.
Numerous clinical conditions, including complex regional pain syndrome, are characterized by autonomic dysfunctions (e.g. altered thermoregulation, sometimes confined to a single limb), and disrupted cortical representation of the body and the surrounding space. The presence, in patients with complex regional pain syndrome, of a disruption in spatial perception, bodily ownership and thermoregulation led us to hypothesize that impaired spatial perception might result in a spatial-dependent modulation of thermoregulation and bodily ownership over the affected limb. In five experiments involving a total of 23 patients with complex regional pain syndrome of one arm and 10 healthy control subjects, we measured skin temperature of the hand with infrared thermal imaging, before and after experimental periods of either 9 or 10 min each, during which the hand was held on one or the other side of the body midline. Tactile processing was assessed by temporal order judgements of pairs of vibrotactile stimuli, delivered one to each hand. Pain and sense of ownership over the hand were assessed by self-report scales. Across experiments, when kept on its usual side of the body midline, the affected hand was 0.5 ± 0.3°C cooler than the healthy hand (P < 0.02 for all, a common finding in cold-type complex regional pain syndrome), and tactile stimuli delivered to the healthy hand were prioritized over those delivered to the affected hand. Simply crossing both hands over the midline resulted in (i) warming of the affected hand (the affected hand became 0.4 ± 0.3°C warmer than when it was in the uncrossed position; P = 0.01); (ii) cooling of the healthy hand (by 0.3 ± 0.3°C; P = 0.02); and (iii) reversal of the prioritization of tactile processing. When only the affected hand was crossed over the midline, it became warmer (by 0.5 ± 0.3°C; P = 0.01). When only the healthy hand was crossed over the midline, it became cooler (by 0.3 ± 0.3°C; P = 0.01). The temperature change of either hand was positively related to its distance from the body midline (pooled data: r = 0.76, P < 0.001). Crossing the affected hand over the body midline had small but significant effects on both spontaneous pain (which was reduced) and the sense of ownership over the hand (which was increased) (P < 0.04 for both). We conclude that impaired spatial perception modulated temperature of the limbs, tactile processing, spontaneous pain and the sense of ownership over the hands. These results show that complex regional pain syndrome involves more complex neurological dysfunction than has previously been considered.
RS: very cool research unravelling the complex mechanisms that underpin CRPS