Andrea Westermann

Sensory signs in complex regional pain syndrome and peripheral nerve injury.

Summary QST revealed more similarities than differences between CRPS‐I, CRPS‐II, and PNI: sensory loss occurred in 63% of CRPS‐I and sensory gain in 81% of PNI patients. Abstract This study determined patterns of sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper‐limb CRPS‐I (n = 298), CRPS‐II (n = 46), and PNI (n = 72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%–69%) exhibited a combination of sensory loss and gain. Patients with CRPS‐I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS‐II patients shared features of CRPS‐I and PNI. CRPS‐I and CRPS‐II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS‐II. In CRPS‐I and ‐II, cold hyperalgesia/allodynia (28%–31%) and dynamic mechanical allodynia (24%–28%) were less frequent than heat or pressure hyperalgesia (36%–44%, 67%–73%), and mechanical hypoesthesia (31%–55%) was more frequent than thermal hypoesthesia (30%–44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS‐I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS‐I and CRPS‐II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research.

Lidocaine patch (5%) produces a selective, but incomplete block of Aδ and C fibers

Summary Topical lidocaine (5%) induced a selective, but only partial blockade of Ad‐ and C‐fibers of variable magnitude in healthy subjects, with significantly increased thermal detection and mechanical pain thresholds and decreased mechanical pain sensitivity. Abstract Topical lidocaine (5%) leads to sufficient pain relief in only 29%–80% of treated patients, presumably by small‐fiber block. The reasons for nonresponse are unclear; it may be due to different underlying pain mechanisms or partly insufficient anesthetic effect. Using quantitative sensory testing (QST) following the protocol of the DFNS (German Research Network on Neuropathic Pain), this study aims to assess the type and extent of somatosensory changes after lidocaine application in healthy volunteers. Twenty‐six healthy volunteers underwent QST on the volar forearm, including thermal and mechanical detection and pain thresholds, twice before (for baseline retest reliability) and once after 6‐hour simultaneous application with lidocaine patch 5% and contralateral placebo in a double‐blinded manner. Pre and post differences of QST parameters were analyzed by paired t‐test (Bonferroni‐corrected alpha 0.0023). QST profiles did not change between the 2 baseline measurements and after the placebo application. Lidocaine application led to a significant change of only the small‐fiber‐associated thresholds (increase of thermal detection and mechanical pain thresholds, decrease of mechanical pain sensitivity). Tactile detection thresholds representing Aβ function remained unchanged. Interindividually, the extent of the small‐fiber block varied widely (eg, thermal detection thresholds: in 54% of the subjects there were only minimal changes; in only 8% were there changes of >60% of the maximal achievable value). Topical lidocaine (5%) induces thermal hypoesthesia and pinprick hypoalgesia, suggesting an isolated but only partial block of Aδ and C fibers of unpredictable extent. Further studies must analyze the influencing factors and determine whether patients with poor analgesic effect, in particular, are those with insufficient small‐fiber block.

Neuropathic pain: is quantitative sensory testing helpful?

Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system and is characterised by a combination of positive and negative sensory symptoms. Quantitative sensory testing (QST) examines the sensory perception after application of different mechanical and thermal stimuli of controlled intensity and the function of both large (A-beta) and small (A-delta and C) nerve fibres, including the corresponding central pathways. QST can be used to determine detection, pain thresholds and stimulus–response curves and can thus detect both negative and positive sensory signs, the second ones not being assessed by other methods. Similarly to all other psychophysical tests QST requires standardised examination, instructions and data evaluation to receive valid and reliable results. Since normative data are available, QST can contribute also to the individual diagnosis of neuropathy, especially in the case of isolated small-fibre neuropathy, in contrast to the conventional electrophysiology which assesses only large myelinated fibres. For example, detection of early stages of subclinical neuropathy in symptomatic or asymptomatic patients with diabetes mellitus can be helpful to optimise treatment and identify diabetic foot at risk of ulceration. QST assessed the individual’s sensory profile and thus can be valuable to evaluate the underlying pain mechanisms which occur in different frequencies even in the same neuropathic pain syndromes. Furthermore, assessing the exact sensory phenotype by QST might be useful in the future to identify responders to certain treatments in accordance to the underlying pain mechanisms.

Different underlying pain mechanisms despite identical pain characteristics: a case report of a patient with spinal cord injury.

Pain following spinal cord injury has been classified as nociceptive (musculoskeletal, visceral) or neuropathic (above, at, below level). There is no clear relation between the etiology and reported symptoms. Thus, due to different underlying mechanisms, the treatment is often ineffective. We report on a patient with spinal cord injury with neurological level of injury at T8 suffering from bilateral burning and prickling pain in the T9-11 dermatomes bilaterally (at-level pain), as well as diffusely in both legs from below the torso (below-level pain), accompanied by musculoskeletal low back pain. Bilateral comparison of quantitative sensory testing (QST) and skin biopsy revealed completely different findings in the dermatome T9 despite identical at-level pain characteristics. On the right side, QST revealed a normal sensory profile; the intraepidermal nerve fiber density (IENFD) was reduced, but not as severe as the contralateral side. On the left side there was a severe sensory loss with a stronger reduction of the IENDF, similar to the areas below the neurological level. These findings were significantly related to the treatment results. Pregabalin induced unilateral pain relief only in the area with remaining sensory function, whereas the left-sided at-level pain was unchanged. Thus, 2 different underlying mechanisms leading to bilaterally neuropathic pain with identical symptoms and with different treatment success were demonstrated in a single patient. The at-level pain in areas with remaining sensory function despite IENFD reduction could be relieved by pregabalin. Thus, in an individual case, QST may be helpful to better understand pain-generating mechanisms and to initiate successful treatment.

Comparison of muscle and joint pressure-pain thresholds in patients with complex regional pain syndrome and upper limb pain of other origin

Summary Pressure‐pain thresholds measured over distal hand joints are highly specific for complex regional pain syndrome and might be a clinical sign reflecting bone pathophysiology. ABSTRACT Pain localized in the deep tissues occurs frequently in complex regional pain syndrome (CRPS). In addition, hyperalgesia to blunt pressure over muscles is common in CRPS, but it often appears in limb pain of other origin as well. Considering that 3‐phase bone scintigraphy (TPBS) reveals periarticular enhanced bone metabolism in CRPS, joint‐associated hyperalgesia to blunt pressure might be a more specific finding than hyperalgesia over muscles. In 34 patients with upper limb pain (18 CRPS, 16 non‐CRPS; diagnosed in accordance to the Budapest criteria) and in 18 healthy controls, pressure‐pain thresholds (PPT) were assessed bilaterally over the thenar (PPTThenar), the metacarpophalangeal (PPTMCP), and the proximal interphalangeal (PPTPIP) joints using a pressure algometer (Somedic, Sweden). Beforehand, all patients had received TPBS for diagnostic purposes independently of the study. Region‐of‐interest (ROI) ratios (mineralization phase) for the MCP and PIP, excluding fracture sites, were correlated with the PPT. In CRPS, all ROI ratios were significantly increased and all PPT of the affected hand were decreased compared to non‐CRPS (PPTThenar: 243 ± 150 kPa vs 358 ± 197 kPa, PPTMCP: 80 ± 67 kPa vs 159 ± 93 kPa, PPTPIP: 80 ± 56 kPa vs 184 ± 110 kPa; P < .01) and controls (PPTThenar: 478 ± 106 kPa, PPTMCP: 254 ± 50 kPa, PPTPIP: 275 ± 76 kPa; P < .01). A PPTThenar below 293 kPa revealed 77% sensitivity but only 63% specificity, whereas a PPTPIP below 102 kPa had 82% sensitivity and 94% specificity to identify CRPS. Only in CRPS were PPTMCP and PPTPIP correlated significantly inversely with the ROI ratio (MCP: r = −0.439, PIP: r = −0.447). PPTPIP shows higher specificity for CRPS type I than PPTThenar without loss of sensitivity. Therefore, measurement of joint PPT could be a noninvasive diagnostic tool reflecting increased bone metabolism assessed by TPBS as a sign of bone pathophysiology.

Are sympathetic blocks useful for diagnostic purposes

Background: Sympathetically maintained pain (SMP) can occur in patients with neuropathic pain. Sympathetically maintained pain is frequently diagnosed clinically by assessing the analgesic effect of an appropriate sympathetic block (SB). The diagnostic value of such blocks depends on both the degree of sympathetic activity disruption achieved and its duration without unintentional concomitant sensory block. Methods: This pilot study evaluated the rate of diagnostically valuable SBs performed by experienced anesthesiologists in 19 patients (stellate/thoracic blocks: n = 11, lumbar blocks: n = 12). Monitoring included pain rating before SB; 10 and 30 minutes; and at 1, 3, and 6 hours after SB; bilateral skin temperature 30 minutes before SB through 120 minutes after SB; and detection of bilateral thresholds for cold, warmth, tactile, and vibration stimuli before and after. Results: Ten (43%) of 23 SBs were not eligible for SMP diagnosis (4 had insufficient skin temperature increase; and 6 had cold or tactile detection threshold increases in the painful area). In 11 of the SBs, no significant sensory threshold change was detected; however, 2 individuals demonstrated marked reductions in the cold or tactile sensory thresholds. Sympathetically maintained pain was diagnosed in 3 (25%) of the 12 patients who had at least 1 SB with the required skin temperature increase without concomitant somatosensory block. Conclusions: Sympathetic blocks are useful in the diagnosis of SMP. However, their value is limited by the potential for false positives (unintentional sensory block) or false negatives (insufficient SB). Adequate monitoring of the sympathetic and somatosensory function for a minimum of 90 minutes after the intervention is essential to ensure that a valid diagnosis of SMP is made.

Association between wind-up ratio and central serotonergic function in healthy subjects and depressed patients

Temporal summation of C-fiber evoked responses generates an increase in action potential discharge in second-order neurons and in perceived pain intensity (wind-up). This may be related to the central serotonergic system which modulates and partly inhibits sensory input. Aim of the study was to investigate the relationship between wind-up and serotonergic activity using loudness dependence of auditory evoked potentials (LDAEP). 18 healthy subjects were compared to 18 patients with major depression, a disease with a putative serotonin deficit. They were examined with quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain (DFNS), including the wind-up ratio (WUR), LDAEP, and psychometric measurements. We found a slight positive correlation between WUR and LDAEP both in healthy controls and depressed patients combined (r=0.340, p=0.043), indicating that WUR may be modulated by serotonergic activity. It can be concluded that inhibitory control to noxious stimuli is partly associated with the central serotonergic function as indicated by LDAEP.

Changes of the Sensory Abnormalities and Cortical Excitability in Patients with Complex Regional Pain Syndrome of the Upper Extremity After 6 Months of Multimodal Treatment.

Objective. The most prominent sensory sign of the complex regional pain syndrome (CRPS) is blunt hyperalgesia, but longitudinal studies on its relation to the outcome of long-term multimodal treatment are lacking. Methods. We examined 24 patients with CRPS type I using standardized Quantitative Sensory Testing on the affected hand and the contralateral hand at baseline and 6 months following treatment. Somatosensory evoked potentials after single and paired-pulse stimulation of the median nerve were performed to assess the paired-pulse suppression (n = 19). Treatment response at follow-up was defined as pain relief > 30% and improved hand function. Statistics: Wilcoxon test, Pearson correlation. Results. At baseline, similar to previous studies, the pressure pain threshold (PPT) was significantly decreased and the pain response to repeated pinprick stimuli was significantly increased, while all detection thresholds were within the normal range without any difference between the later treatment responders and non-responders. After 6 months of treatment, the PPT increased significantly in the whole study group. However, the pressure hyperalgesia improved only in treatment responders (n = 17, P < 0.05), whereas there was no improvement in non-responders (n = 7). The rest of the sensory profile remained nearly unchanged. There was a correlation between the paired-pulse suppression and the PPT only at follow-up (r = 0.49, P < 0.05), but not at baseline, where low pressure pain threshold was associated with impaired paired-pulse suppression. Conclusion. Thus, the persistence of blunt hyperalgesia seems to be associated with impaired paired-pulse suppression, both representing maladaptive central nervous changes in CRPS, which may account for the treatment non-response in this subgroup.