Exaggeration of tissue trauma induces signs and symptoms of acute CRPS I, however displays distinct differences to experimental CRPS II

Gradl, Georg; Gaida, Susanne; Finke, B.; Gierer, Philip; Mittlmeier, Thomas; Vollmar, Brigitte

doi:10.1016/j.neulet.2006.04.007

Cited by 18 publications

(3 citation statements)

References 21 publications

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“…In the present study, PEA-MPS treatment decreased PARP activity. Finally, tissue apoptosis may serve as a marker for CRPS-I [41, 42]. Our data show that PEA-MPS treatment reduced tibia fracture-induced Bax expression and increased Bcl-2 expression that was reduced in tibia fracture mice.…”

Section: Discussionmentioning

confidence: 75%

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome

et al. 2017

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Complex regional pain syndrome type 1 (CRPS-I) is a disabling and frequently chronic condition. It involves the extremities and is a frequent consequence of distal tibia and radius fractures. The inflamed appearance of the affected CRPS-I limb suggests that local production of inflammatory mediators may be implicated in the ensuing etiology. A rodent tibia fracture model, characterized by inflammation, chronic unilateral hindlimb warmth, edema, protein extravasation, allodynia and hyperalgesia resembles the clinical features of patients with acute CRPS-I. N-palmitoylethanolamine (PEA), a member of the family of naturally-occurring N-acylethanolamines, is well-known for its ability to modulate inflammatory processes and regulate pain sensitivity. However, the large particle size and lipidic nature of PEA may limit its bioavailability and solubility when given orally. Micronized formulations are frequently used to enhance the dissolution rate of drug and reduce its variability of absorption when orally administered. The aim of this study was to assess the effects of a formulation of micronized and ultramicronized PEA (PEA-MPS), given orally in a mouse model of CRPS-I. CD-1 male mice were subjected to distal tibia fracture and divided into two groups: control and treated with PEA-MPS (PEA micronized 300 mg/kg and ultramicronized 600 mg/kg). Sensibility to pain was monitored in all mice throughout the course of the experiment. Twenty-eight days after tibia fracture induction animals were sacrificed and biochemical parameters evaluated. The PEA-MPS-treated group showed an improved healing process, fracture recovery and fibrosis score. PEA-MPS administration decreased mast cell density, nerve growth factor, matrix metalloproteinase 9 and cytokine expression. This treatment also reduced (poly-ADP)ribose polymerase activation, peroxynitrite formation and apoptosis. Our results suggest that PEA-MPS may be a new therapeutic strategy in the treatment of CRPS-I.

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Section: Discussionmentioning

confidence: 75%

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome

et al. 2017

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“…Models which have been rarely used are the combination of spinal nerve ligation (SNL) and knee joint immobilization 98 , soft tissue trauma plus an intra-arterial perfusion of muscle tissue supernatant 48 or the intra-arterial infusion of free radical donors. 131…”

Section: Overviewmentioning

confidence: 99%

The Rodent Tibia Fracture Model: A Critical Review and Comparison With the Complex Regional Pain Syndrome Literature

Birklein

Ibrahim

Schlereth

et al. 2018

The Journal of Pain

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“…Several hypotheses about the pathophysiology of CRPS have been proposed emphasizing the importance of peripheral neurogenic inflammation [10], [11], small-fibre axonal degeneration [12], [13] or central changes (cortical reorganisation) [14]–[16] similar to other pain disorders [17], since cortical changes were related to measures of pain plasticity (hyperalgesia) rather than spontaneous pain [14], [15]. Others suggested an interaction of peripheral and central nervous changes [18].…”

Section: Introductionmentioning

confidence: 99%

Interaction of Hyperalgesia and Sensory Loss in Complex Regional Pain Syndrome Type I (CRPS I)

et al. 2008

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BackgroundSensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group.Methods61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed.ResultsIn acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb.ConclusionsWe propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

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Exaggeration of tissue trauma induces signs and symptoms of acute CRPS I, however displays distinct differences to experimental CRPS II

Cited by 18 publications

References 21 publications

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome

The Rodent Tibia Fracture Model: A Critical Review and Comparison With the Complex Regional Pain Syndrome Literature

Interaction of Hyperalgesia and Sensory Loss in Complex Regional Pain Syndrome Type I (CRPS I)

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