Welcome to the May research update – see more at www.crpsuk.com
Pain Physician. 2012 May;15(3):255-66.
Skin biopsy in complex regional pain syndrome: case series and literature review.
Kharkar S, Venkatesh YS, Grothusen JR, Rojas L, Schwartzman RJ.
Accumulating experimental and clinical evidence supports the hypothesis that complex regional pain syndrome type I (CRPS-I) may be a small fiber neuropathy.
To evaluate the use of commercially available standard biopsy methods to detect intradermal axon pathology in CRPS-I, and to ascertain if these structural changes can explain quantitative sensory testing (QST) findings in CRPS-I.
Retrospective review of charts and laboratory data.
Skin biopsies from 43 patients with CRPS-I were stained with PGP 9.5, and epidermal nerve fiber density, sweat gland nerve fiber density and morphological abnormalities were evaluated. Thirty-five patients had quantitative sensory testing.
Alterations in skin innervation were seen in approximately 20% of CRPS-I patients with commercial processing. There were no patient characteristics, including duration of disease, that predicted a decreased epidermal nerve fiber density (ENFD). There was no consistent relationship between QST changes and ENFD measured by standard commercial skin biopsy evaluation procedures.
Commercial processing of tissue does not utilize stereologic quantitative analysis of nerve fiber density. Biopsy material is utilized from a proximal and distal source only, and differences in denervation of a partial nerve territory may be missed. The functional attributes of small fibers cannot be assessed.
The negative results indicate that CRPS-I may be associated with changes in the ultramicroscopic small fiber structure that cannot be visualized with commercially available techniques. Alternatively, functional rather than structural alterations of small fibers or pathological changes at a more proximal site such as the spinal cord or brain may be responsible for the syndrome.
Curr Pharm Des. 2012 May 16. [Epub ahead of print]
Immunological Aspects of the Complex Regional Pain Syndrome (CRPS).
Limb trauma can lead to the development of a complex regional pain syndrome (CRPS). CRPS is a descriptive term of a variety of different symptoms. According to the current IASP-approved criteria, human CRPS can be diagnosed if a combination of signs is present: continuing pain and hyperalgesia, disproportionate to the initial trauma, skin temperature and colour asymmetry, sweating asymmetry, edema, decreased range of motion, and trophic changes. The diagnosis and treatment of human CRPS can be demanding and the pathophysiology underlying the disease is still under investigation. Immunological aspects are considered to play an important role in the development of CRPS. The impact of elevated pro-inflammatory cytokines systemically as well as locally, increased neurogenic inflammation and auto-antibodies in the pathophysiological development of CRPS are discussed in this review.
Curr Med Res Opin. 2012 May 2. [Epub ahead of print]
Topical pain management with the 5% lidocaine medicated plaster – a review.
Mick G, Correa-Illanes G.
Abstract Background: The topical 5% lidocaine medicated plaster is recommended as first-line treatment for localized peripheral neuropathic pain. Scope: In order to provide an overview of the efficacy and safety of the lidocaine plaster in the treatment of different neuropathic pain conditions, all efficacy and safety studies (randomized, controlled, or open-label with well described methodology), case reports, and pharmacological studies on the lidocaine plaster retrieved from a PubMed literature research (1960 – March 2012) plus additional references identified from retrieved articles were included. Findings: The lidocaine plaster is efficacious in the treatment of neuropathic pain symptoms associated with previous herpes zoster infection. Results from a large open-label controlled study suggest that the lidocaine plaster could be at least as effective as systemic pregabalin in the treatment of postherpetic neuralgia and painful diabetic polyneuropathy. Open-label studies indicate efficacy in the treatment of other localized neuropathic pain conditions, such as painful idiopathic sensory polyneuropathy, complex regional pain syndrome, carpal tunnel syndrome sequelae, postsurgical and posttraumatic pain. Quality of life markedly improved in a variety of neuropathic pain conditions and long-term treatment provided sustained relief in patients with neuropathic pain who are responsive to lidocaine plaster. The lidocaine plaster is usually well tolerated. The risk of systemic adverse events and pharmacokinetic interactions with concomitant medication is minimal owing to low systemic exposure. Conclusions: Treatment of several, primarily neuropathic and mixed-pain conditions with the 5% lidocaine medicated plaster was found efficacious and safe. Further controlled studies, in particular where only small open-label studies or case reports are available, should be considered.
A possible case of complex regional pain syndrome of the nose?
Faraj-Hakim S, Bleys RL, Buwalda J, de Ru JA.
We present a case report of a patient with a putative diagnosis of complex regional pain syndrome of the nose. We would like to bring this disorder to the attention of rhinologists.
A 53-year-old man presented with a history of extreme, constant, debilitating pain in his nose that started after he underwent several extensive nasal surgeries. Examination revealed atrophic nasal mucous membranes at the nasal septum. No other abnormalities were found. The pain did not diminish despite administration of analgesics and neuropathic pain medications. We propose a diagnosis of complex regional pain syndrome of the nose.
The large number of nasal surgeries performed worldwide and the far reaching consequences of this debilitating syndrome indicate that it merits further investigation to determine whether it is a distinct disorder that should be recognized as such.
J Neurosci. 2012 Apr 25;32(17):5747-56.
Abnormalities in hippocampal functioning with persistent pain.
Mutso AA, Radzicki D, Baliki MN, Huang L, Banisadr G, Centeno MV, Radulovic J, Martina M, Miller RJ, Apkarian AV.
Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice compared with Sham animals exhibited hippocampal (1) reduced extracellular signal-regulated kinase expression and phosphorylation, (2) decreased neurogenesis, and (3) altered short-term synaptic plasticity. To relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared with controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.
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