Complex interaction of sensory and motor signs and symptoms in chronic CRPS.

Spontaneous pain, hyperalgesia as well as sensory abnormalities, autonomic, trophic, and motor disturbances are key features of Complex Regional Pain Syndrome (CRPS). This study was conceived to comprehensively characterize the interaction of these symptoms in 118 patients with chronic upper limb CRPS (duration of disease: 43±23 months). Disease-related stress, depression, and the degree of accompanying motor disability were likewise assessed. Stress and depression were measured by Posttraumatic Stress Symptoms Score and Center for Epidemiological Studies Depression Test. Motor disability of the affected hand was determined by Sequential Occupational Dexterity Assessment and Michigan Hand Questionnaire. Sensory changes were assessed by Quantitative Sensory Testing according to the standards of the German Research Network on Neuropathic Pain. Almost two-thirds of all patients exhibited spontaneous pain at rest. Hand force as well as hand motor function were found to be substantially impaired. Results of Quantitative Sensory Testing revealed a distinct pattern of generalized bilateral sensory loss and hyperalgesia, most prominently to blunt pressure. Patients reported substantial motor complaints confirmed by the objective motor disability testings. Interestingly, patients displayed clinically relevant levels of stress and depression. We conclude that chronic CRPS is characterized by a combination of ongoing pain, pain-related disability, stress and depression, potentially triggered by peripheral nerve/tissue damage and ensuing sensory loss. In order to consolidate the different dimensions of disturbances in chronic CRPS, we developed a model based on interaction analysis suggesting a complex hierarchical interaction of peripheral (injury/sensory loss) and central factors (pain/disability/stress/depression) predicting motor dysfunction and hyperalgesia

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I)

Sensory 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

Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain

a b s t r a c t Background: NMDA receptors are involved in the development and maintenance of neuropathic pain. We evaluated the efficacy and safety of intranasal (S)-ketamine, one of the most potent clinically available NMDA receptor antagonists. Methods: Sixteen patients with neuropathic pain of various origins were randomized into two treatment groups: (S)-ketamine 0.2 mg/kg (group 1); (S)-ketamine 0.4 mg/kg (group 2). Plasma concentrations of (S)-ketamine and (S)-norketamine were measured over 6 h by High Performance Liquid Chromatography combined with mass spectrometry. Quantitative sensory testing (QST) was conducted before, during and after treatment. Side effects and amount of pain reduction were recorded. Results: Intranasal (S)-ketamine administration lead to peak plasma concentrations of 27.7 ± 5.9 ng/ml at 10 ± 6.3 min (group 1) and 34.3 ± 22.2 ng/ml at 13.8 ± 4.8 min after application (group 2). Maximal plasma concentrations of (S)-norketamine were 18.3 ± 14.9 ng/ml at 81 ± 59 min (group 1) and 34.3 ± 5.5 ng/ml at 75 ± 40 min (group 2). Pain scores decreased significantly in both groups with minimal pain at 60 min after drug administration (70 ± 10% and 61 ± 13% of initial pain in groups 1 and 2). The time course of pain decrease was significantly correlated with plasma concentrations of (S)-ketamine and (S)-norketamine (partial correlations: (S)-norketamine: À0.90 and À0.86; (S)-ketamine: À0.72 and À0.71 for group 1 and group 2, respectively). Higher dosing elicited significantly more side effects. Intranasal (S)-ketamine had no significant impact on thermal or mechanical detection and pain thresholds in normal or symptomatic skin areas. Conclusions: Intranasal administration of low dose (S)-ketamine rapidly induces adequate plasma concentrations of (S)-ketamine and subsequently of its metabolite (S)-norketamine. The time course of analgesia correlated with plasma concentrations

Patient disposition.

<p>Disposition of patients eligible for the study. Eligible patients had been treated at the pain clinic and were diagnosed with chronic CRPS (Duration of disease more than 12 months).</p

Impairment of hand motor function.

<p>Bars display the percentage of patients displaying the respective motor impairment. Significance: * p<0.001 ipsilateral vs. contralateral hand, Wilcoxon signed ranks method test.</p

Thermal pain thresholds in acute and chronic CRPS.

<p>Cold pain thresholds (A) and heat pain thresholds (B) are significantly lowered in acute CRPS (corresponding to cold and heat hyperalgesia). Pain partially (cold pain) or totally (heat pain) recovers to normal in chronic CRPS. Significant increases of similar magnitude are also found in the contralateral “unaffected” hand for heat pain (B) and to a lesser extent in cold pain (A). Significance vs. controls: *** p<0.001; Significance vs. acute CRPS: ⁺⁺⁺ p<0.001; Significance vs. ipsilateral hand: ^(§) p<0.10, ^§ p<0.05. Note: Significance marks that bridge symbols of ipsilateral and contralateral hands apply to both hands. Error bars show 1SEM.</p

Proposed modified research diagnostic criteria for CRPS.^*

<p>*<i>Bruehl S, Harden RN, Galer BS et al. External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain 1999; 81: 147–154.</i></p

Number of traumatic memories.

<p>Number of traumatic memories.</p

Standardized comparison of QST data normalized to mean and standard deviation of the control group (z-normalisation).

<p>A: Somatosensory profile of thermal and mechanical thresholds: Thermal Detection Thresholds: CDT: Cold Detection Threshold; WDT: Warm Detection Threshold; TSL: Thermal Sensory Limen. Thermal Pain Thresholds: CPT: Cold Pain Threshold; HPT: Heat Pain Threshold. Mechanical Pain Thresholds: PPT: Pressure Pain Threshold; MPT: Mechanical Pain Threshold; MPS: Mechanical Pain Sensitivity; WUR: Wind-up ratio. Mechanical Detection Thresholds: MDT: Mechanical Detection Threshold; VDT: Vibration Detection Threshold. B: PHS: Paradoxical Heat Sensation (PHS); Dynamic Mechanical Allodynia (DMA). Significance: ipsilateral hand vs. control: * p<0.05. Significance contralateral hand vs. control: + p<0.05. Patients with chronic CRPS displayed a bilateral hyperalgesia in every painful somatosensory modality as well as bilateral somatosensory loss.</p