Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome.

PURPOSE: Several articles have claimed that complex regional pain syndrome (CRPS) does not exist. Although a minority view, it is important to understand the arguments presented in these articles. We conducted a systematic literature search to evaluate the methodological quality of articles that claim CRPS does not exist. We then examined and refuted the arguments supporting this claim using up-to-date scientific literature on CRPS. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane CENTRAL databases. Inclusion criteria for articles were (a) a claim made that CRPS does not exist or that CRPS is not a distinct diagnostic entity and (b) support of these claims with subsequent argument(s). The methodological quality of articles was assessed if possible. RESULTS: Nine articles were included for analysis: 4 narrative reviews, 2 personal views, 1 letter, 1 editorial and 1 case report. Seven points of controversy were used in these articles to argue that CRPS does not exist: 1) disagreement with the label "CRPS"; 2) the "unclear" pathophysiology; 3) the validity of the diagnostic criteria; 4) CRPS as a normal consequence of immobilization; 5) the role of psychological factors; 6) other identifiable causes for CRPS symptoms; and 7) the methodological quality of CRPS research. CONCLUSION: The level of evidence for the claim that CRPS does not exist is very weak. Published accounts concluding that CRPS does not exist, in the absence of primary evidence to underpin them, can harm patients by encouraging dismissal of patients' signs and symptoms.

Laser-evoked potentials in painful radiculopathy.

OBJECTIVE: The aims of this exploratory study were (1) to develop a standardized objective electrophysiological technique with laser-evoked potentials to assess dorsal root damage quantitatively and (2) to correlate these LEP measures with clinical parameters and sensory abnormalities (QST) in the affected dermatome. METHODS: Thirty-eight patients with painful radiculopathy and 20 healthy subjects were investigated with LEP recorded from the affected dermatome and control areas as well as with quantitative sensory testing. Questionnaires evaluating severity and functionality were applied. RESULTS: On average, LEP amplitudes and latencies from the affected dermatomes did not differ from the contralateral control side. In patients with left L5 radiculopathy (more severely affected) the N2 latency was longer and the amplitudes reduced. CONCLUSIONS: The N2P2 amplitude correlated with pinprick evoked sensations in QST. The N2 latency from the affected dermatome correlates with pain intensity, chronicity, clinical severity and with a decrease of physical function. SIGNIFICANCE: An increase in N2-latency indicates a more pronounced nerve root damage, which is associated with a decrease of function and an increase of severity and pain. LEP amplitudes are associated with the functional status of the nociceptive system and may distinguish between degeneration of neuronal systems and central sensitization processes.

Prediction of response to tapentadol in chronic low back pain.

BACKGROUND: Many chronic low back pain (cLBP) patients do not satisfactorily respond to treatment. The knowledge of responders and non-responders before initiating treatment would improve decision making and reduce health care costs. The aims of this exploratory prediction study in cLBP patients treated with tapentadol were to identify predictors of treatment outcome based on baseline characteristics, to evaluate quality-of-life and functionality as alternative outcome parameters and to develop nomograms to calculate the individual probability of response. METHODS: In a retrospective analysis of an open-label phase 3b trial, 46 baseline characteristics were included into statistical prediction modelling. One hundred and twenty-one patients were followed up during the titration and treatment period and 67 patients were analysed who discontinued the trial. RESULTS: Demographic data were not relevant for response prediction. Nine baseline co-variables were robust: painDETECT score, intensity of burning and painful attacks, SF36 Health Survey score (MCS, PCS), EuroQol-5, Hospital Anxiety/Depression Scale. Gender had a minor influence. Alternative outcomes (quality-of-life, functionality) were more important for response prediction than conventional pain intensity measures. Neuropathic symptoms (high painDETECT score) had a positive predictive validity. Painful attacks and classical yellow flags (depression, anxiety) negatively influenced the treatment response. High depression scores, female gender and low burning predicted discontinuation during titration. CONCLUSION: In this exploratory study, predictive baseline characteristics have been identified that can be used to calculate the individual probability of tapentadol response in cLBP. The small sample size in relation to the number of initial variables is a limitation of this approach. SIGNIFICANCE: Predictors for treatment response of tapentadol were identified in patients with chronic low back pain based on clinical pre-treatment characteristics that can guide personalized treatment. Quality-of-life and functionality were the most relevant outcomes for response prediction.

Influence of intraoperative remifentanil and sufentanil on sensory perception: a randomized trial.

OBJECTIVE: The clinical relevance of pro- and hyperalgesic effects of opioids is still a matter of debate. Particularly for remifentanil, an increased postoperative need for analgesics has been demonstrated suggesting opioid-induced hyperalgesia as a possible cause. The aim of the study was therefore to investigate the effect of intraoperatively applied remifentanil compared to sufentanil on somatosensory thresholds investigated with the quantitative sensory testing (QST) battery of the German Research Network on Neuropathic Pain (DFNS). RESEARCH DESIGN AND METHODS: Twenty-three patients undergoing surgery of the female breast were randomly assigned to intraoperative remifentanil (0.4 µg × kg-1 × min-1) or sufentanil (0.25 µg × kg-1 bolus, 0.15 µg × kg-1, repetition after 60 min) application. Anesthesia was maintained BIS-guided (Bispectral indexTM) with propofol and postoperative analgesia was ensured with paracetamol (max. 3 g/24 h). Quantitative sensory testing was performed in the region of dermatome Th 5 in the mid-axillary line preoperatively and 20 h postoperatively. CLINICAL TRIAL REGISTRATION: The study was registered at the German registry for clinical studies (DRKS00009002). MAIN OUTCOME MEASURES: Comparison of somatosensory thresholds before versus after surgery and application of intraoperative remifentanil or sufentanil. RESULTS: Sixteen patients could be finally included in the analysis. No differences of mechanical or thermal detection or pain thresholds were observed between pre- and postoperative testing or between remifentanil and sufentanil. CONCLUSION: A change of somatosensory thresholds or a clinically relevant opioid-induced hyperalgesia in the selected small patient sample (segmental resections or mastectomy with or without sentinel lymph node biopsy, surgery length <90 minutes, sufficient postoperative pain medication with paracetamol due to rather low postoperative pain intensities) with remifentanil or sufentanil was not detected 20 h after surgery.

Dynamic cerebral autoregulation in stroke patients with a central sympathetic deficit.

OBJECTIVE: To investigate the functional role of the sympathetic innervation on cerebral autoregulation. MATERIALS AND METHODS: Seventeen patients with infarction of the dorsolateral medulla oblongata affecting central sympathetic pathways (Wallenberg's syndrome) and 21 healthy controls were included in the study. Cerebral blood flow velocity (CBFV) in the medial cerebral artery was investigated using transcranial Doppler ultrasound during decrease in cerebral perfusion pressure induced by leg-cuff test and tilt table. RESULTS: Upon leg-cuff test, changes of cerebral blood flow and mean arterial blood pressure as well as autoregulatory index did not differ between patients or controls. No differences were found in changes of CBFV, mean arterial blood pressure and heart rate between patients or controls during the tilt table test. CONCLUSIONS: We suggest that the sympathetic nervous system does not have an influence on cerebral autoregulation after decrease in perfusion pressure under normotonous conditions.

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes.

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.

Somatosensory function in asymptomatic Parkin-mutation carriers.

BACKGROUND AND PURPOSE: It is a matter of debate whether somatosensory abnormalities in Parkinson's disease (PD) precede or follow PD motor signs and whether they are of central or peripheral origin. The sensory sural nerve action potential amplitude (SNAP) was previously reported to be reduced in symptomatic Parkin-associated PD. The aim of our study was to investigate asymptomatic Parkin-mutation carriers to elucidate whether putative somatosensory abnormalities precede motor symptoms therewith helping to determine the origin of somatosensory signs. METHODS: Nine subjects with Parkin-mutations and nine healthy controls were examined clinically, with quantitative sensory testing (QST) and neurography. RESULTS: There was a higher frequency of cold pain threshold abnormalities and hypofunction of Abeta-fibres/central afferent pathways in Parkin-mutation carriers compared to controls. Neurography of Parkin-mutation carriers did not indicate peripheral neuropathy. CONCLUSIONS: Sensory abnormalities of asymptomatic Parkin-mutation carriers as obtained by QST suggest impairment of either small and large peripheral pathways or central somatosensory processing. In contrast to Parkin-associated PD, asymptomatic Parkin-mutation carriers do not show a reduced SNAP.

Somatosensory processing in a German family with PINK1 mutations: its potential role in Parkinson disease.

BACKGROUND: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia. OBJECTIVE: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. METHODS: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). RESULTS: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. CONCLUSIONS: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.