Bilaterally Reduced Intraepidermal Nerve Fiber Density in Unilateral CRPS-I

Rasmussen, Vinni Faber; Karlsson, Páll; Drummond, Peter D.; Schaldemose, E.L.; Terkelsen, Astrid Juhl; Jensen, Troels Staehelin; Knudsen, Lone

doi:10.1093/pm/pnx240

Cited by 35 publications

(40 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is reported that around 45% and 70% of CRPS-I patients develop signs of thermal and mechanical hypersensitivity, respectively. Thermal and mechanical hypersensitivities are among the major symptoms affecting CRPS-I patients 25,42,43,47. A recent study demonstrated CPIP model rats developed obvious signs of thermal hyperalgesia, which correlates with our present findings.…”

Section: Discussionsupporting

confidence: 90%

<p>Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain</p>

Yin¹,

Hu²,

Liu³

et al. 2019

JPR

View full text Add to dashboard Cite

Purpose: Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition, which remains clinically challenging. The mechanisms of CRPS-I still remain largely unknown. We aim to identify transcriptome profiles of genes relevant to pain mechanisms and major pathways involved in CRPS-I. Methods: A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. RNA-sequencing (RNA-Seq) was used to profile transcriptome of L4-6 dorsal root ganglia (DRGs) of a rat model of CRPS-I. Results: CPIP model rats developed persistent mechanical/thermal hyperalgesia in ipsilateral hind paw. RNA-Seq identified a total of 295 differentially expressed genes (DEGs), including 195 up- and 100 downregulated, in ipsilateral DRGs of CPIP rats compared with sham rats. The expression of several representative genes was confirmed by qPCR. Functional analysis of DEGs revealed that the most significant enriched biological processes of upregulated genes include response to lipopolysaccharide, inflammatory response and cytokine activity, which are all important mechanisms mediating pain. We further screened DEGs implicated in pain progress, genes enriched in small- to medium-sized sensory neurons and enriched in TRPV1-lineage nociceptors. By comparing our dataset with other published datasets of neuropathic or inflammatory pain models, we identified a core set of genes and pathways that extensively participate in CPIP and other neuropathic pain states. Conclusion: Our study identified transcriptome gene changes in DRGs of an animal model of CRPS-I and could provide insights into identifying promising genes or pathways that can be potentially targeted to ameliorate CRPS-I.

show abstract

Section: Discussionsupporting

confidence: 90%

<p>Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain</p>

Yin¹,

Hu²,

Liu³

et al. 2019

JPR

View full text Add to dashboard Cite

show abstract

“…Cutaneous nerve fibres that follow the dermal-epidermal border send terminal 'neurite' twigs into the epidermis. The density of these neurites is reduced in affected skin [23,39] or bilaterally [42] in at least a subgroup of CRPS patients. In the present study, the density of the dermal nerve fibres that supply these neurites was lower in CRPS-affected skin than in controls, and also was reduced on the uninjured side in some patients.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, intra-epidermal nerve fibre density was examined almost exclusively in patients with longstanding CRPS [23,39,42] whereas our sample contained patients with various disease durations, including relatively short periods. Dermal nerve fibre density in the affected limb was unrelated to disease duration or CRPS subtype, suggesting that dermal neuropathology develops soon after injury or perhaps even precedes limb trauma; if, so, this could form part of a CRPS-prone phenotype [4,42]. Warm CRPS often begins earlier in the clinical presentation than cold CRPS, and is associated more strongly than cold CRPS with signs of inflammation [6].…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory signs generally subside within the first year of CRPS, but later on the affected limb may become cold and blue [6]. Skin biopsy studies indicate that CRPS is associated with cutaneous small fibre pathology [23,39,42], but whether this precedes the injury, is caused by injury-associated inflammatory changes or is part of a later neurodegenerative process is unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dermal nerve fibre and mast cell density, and proximity of mast cells to nerve fibres in the skin of patients with complex regional pain syndrome

Morellini

Finch

Göebel

et al. 2018

Pain

View full text Add to dashboard Cite

An interaction between cutaneous nerves and mast cells may contribute to pain in complex regional pain syndrome (CRPS). To explore this, we investigated the density of dermal nerve fibres, and the density and proximity of mast cells to nerve fibres, in skin biopsies obtained from the affected and unaffected limbs of 57 patients with CRPS and 28 site-matched healthy controls. The percentage of the dermis stained by the pan-neuronal marker protein gene-product 9.5 was lower in the affected limb of patients than in controls (0.12 ± 0.01% vs 0.22 ± 0.04%, P < 0.05), indicating a reduction in dermal nerve fibre density. This parameter did not correlate with CRPS duration. However, it was lower in the affected than unaffected limb of patients with warm CRPS. Dermal mast cell numbers were similar in patients and controls, but the percentage of mast cells less than 5 µm from nerve fibres was significantly lower in the affected and unaffected limbs of patients than in controls (16.8 ± 1.7%, 16.5 ± 1.7%, and 31.4 ± 2.3% respectively, P < 0.05). We confirm previous findings of a mild neuropathy in CRPS. Our findings suggest that this either develops very early after injury or precedes CRPS onset. Loss of dermal nerve fibres in CRPS might result in loss of chemotactic signals, thus halting mast cell migration toward surviving nerve fibres. Failure of normal nerve fibre-mast cell interactions could contribute to the pathophysiology of CRPS.

show abstract

“…The second mechanism of itching is neuropathic itch or PHI caused by neural injury in the chronic phase of herpes zoster after the rash has disappeared [10,12]. In neuropathic itch, varicella-zoster virus alleviates and demyelination of nerve fibers in the skin that transmit itch occurs [1], which is similar to neuropathic pain [13,14]. Demyelination of nerve fibers could cause ectopic discharges due to changes in ion channels [15,16], and overexcitation of primary neurons increases the transmission of itch, resulting in intractable neuropathic itch.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin for postherpetic itch: a case report

et al. 2020

View full text Add to dashboard Cite

Background: Postherpetic itch has not commonly received attention as a complication of herpes zoster because pain predominates over itch in most patients with herpes zoster. Most cases of postherpetic itch are mild; however, cases of severe postherpetic itch reducing quality of life are rare. Case presentation: A 52-year-old woman complained of severe itch in her left pinna and cheek 1 month after the first onset of herpes zoster at the same site. Owing to her scratching, she developed ulcers on her left pinna and cheek. Pregabalin was prescribed, and the itch subsided immediately, with the ulcers disappearing within 1 month. Discussion: Severe itch was thought to be caused by neural injury from herpes zoster. Pregabalin may be a useful treatment option for neuropathic itch induced by herpes zoster.

show abstract

Bilaterally Reduced Intraepidermal Nerve Fiber Density in Unilateral CRPS-I

Cited by 35 publications

References 45 publications

<p>Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain</p>

<p>Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain</p>

Dermal nerve fibre and mast cell density, and proximity of mast cells to nerve fibres in the skin of patients with complex regional pain syndrome

Pregabalin for postherpetic itch: a case report

Contact Info

Product

Resources

About