Thomas K. Ringsted

Quantitative sensory testing of persistent pain after video-assisted thoracic surgery lobectomy

BACKGROUND Video-assisted thoracic surgery (VATS) lobectomy may potentially reduce the risk of post-thoracotomy pain syndrome (PTPS). However, it may still carry a risk of intraoperative nerve damage and thereby development of PTPS. Thus, our aim was to present a detailed long-term neurophysiological characterization of PTPS after VATS. METHODS Quantitative sensory testing, using thermal and mechanical stimuli, was performed in 13 PTPS patients and 35 pain-free patients recruited 33 months after VATS lobectomy. RESULTS When comparing the operated side with the control side in PTPS patients, increased thresholds of tactile and warmth detection were observed, while in pain-free patients, increased thresholds of warmth detection, cool detection, and heat pain were demonstrated. At the anterior porthole, pain-free patients displayed increased threshold to thermal detection when compared with the control side. Only side-to-side difference for tactile detection threshold was increased in PTPS patients compared with pain-free patients. Assessment of central sensitization showed no significant differences within or between PTPS and pain-free patients nor did group comparison of area of hypo- and hyperaesthesia to cool. Anxiety and depression scores (HADS) were higher in PTPS patients, but the area of hyper- and hypoaesthesia did not differ significantly between HADS groups. CONCLUSIONS Increased sensory thresholds suggest nerve injury to be present on the operated side in both PTPS and pain-free patients. However, no significant quantitative differences between PTPS and pain-free patients could be found, implicating the presence of factors other than intercostal nerve injury as important for development of PTPS after VATS lobectomy.

Neurophysiological characterization of persistent postthoracotomy pain.

ObjectivesThe postthoracotomy pain syndrome (PTPS) has a prevalence of 30% to 40%. Although intraoperative nerve damage during thoracotomy has been demonstrated, it has not been clearly linked to PTPS and detailed quantitative sensory characterization data have so far not been presented, comparing PTPS and pain-free patients. MethodsNeurophysiological characterization was performed in 17 patients with PTPS and 24 pain-free postthoracotomy patients using a detailed quantitative sensory testing protocol and psychometric questionnaires. ResultsPain and pain-free patients had increased thresholds to tactile detection (P=0.001 and P=0.01) and cool detection (P<0.001 and P<0.01) on the operated side versus the contralateral side. Pain patients also had increased thresholds for warmth detection (P<0.001) and heat pain (P<0.01) on the operated side. The PTPS patients demonstrated increased side-to-side differences for warmth detection (P<0.01), heat pain (P<0.05), and cool detection (P<0.05) thresholds compared with pain-free patients. Pain patients also more frequently experienced cool hyperesthesia (8 of 17 vs. 1 of 24, P<0.01), but no differences were found for pressure pain, temporal summation, or sensory mapping to cool (200 cm2 vs. 76 cm2, P=0.18). Hospital Anxiety and Depression Scale scores were higher for PTPS than for pain-free patients (P<0.01). DiscussionNeurophysiological assessments indicate nerve injury to be common in pain and pain-free patients after thoracotomy. The combination of increased thresholds together with hyperesthesia, suggests consequences of nerve injury to be more pronounced in PTPS patients.

A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0–10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P = 0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [−0.1 to 3.9] and 0.6 [−1.2 to 2.5] fibers/mm, respectively (P = 0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application. Trial Registration Clinicaltrialsregister.eu 2012-001540-22 ClinicalTrials.gov NCT01699854

Does Naloxone Reinstate Secondary Hyperalgesia in Humans after Resolution of a Burn Injury? A Placebo-Controlled, Double-Blind, Randomized, Cross-Over Study

Introduction Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury. Methods Twenty-two healthy volunteers were included in this placebo-controlled, randomized, double-blind, cross-over study. Following baseline assessment of thermal and mechanical thresholds, a first-degree burn injury (BI; 47°C, 7 minutes, thermode area 12.5 cm2) was induced on the lower leg. Secondary hyperalgesia areas around the BI-area, and separately produced by brief thermal sensitization on the contralateral thigh (BTS; 45°C, 3 minutes, area 12.5 cm2), were assessed using a polyamide monofilament at pre-BI and 1, 2, and 3 hours post-BI. At 72 hrs, BI and BTS secondary hyperalgesia areas were assessed prior to start of a 30 minutes intravenous infusion of naloxone (total dose 21 microg/kg) or placebo. Fifteen minutes after start of the infusion, BI and BTS secondary hyperalgesia areas were reassessed, along with mechanical and thermal thresholds. Results Secondary hyperalgesia areas were demonstrable in all volunteers 1–3 hrs post-BI, but were not demonstrable at 72 hrs post-burn in 73–86% of the subjects. Neither magnitude of secondary hyperalgesia areas nor the mechanical and thermal thresholds were associated with naloxone-treated compared to placebo-treated subjects. Conclusion Naloxone (21 microg/kg) did not reinstate secondary hyperalgesia when administered 72 hours after a first-degree burn injury and did not increase BTS-generated hyperalgesia. The negative results may be due to the low dose of naloxone or insufficient tissue injury to generate latent sensitization.

Sensory testing in patients with postthoracotomy pain syndrome: Part 1: mirror-image sensory dysfunction.

Objectives:Mirror-image sensory dysfunction (MISD) has not been systematically characterized in persistent postoperative pain. Methods:The presence of MISD was evaluated with standardized stimuli, in preoperative patients scheduled for a thoracotomy (n=14) and in patients with postthoracotomy pain syndrome [PTPS (n=14)]. The primary outcome was investigation of the areas of sensory dysfunction, evaluated twice by dynamic sensory mapping with metal rollers and a brush. Results:In PTPS patients, sensory dysfunction was present on the surgical side, and in 12 of 14 patients MISD was demonstrated. The total areas of sensory dysfunction [median (interquartile range)] were: day 1, 500 (289 to 636) cm2 and 60 (0 to 379) cm2 on the surgical and nonsurgical side (P<0.005), respectively; and day 2, 355 (266 to 697) cm2 and 81 (0 to 202) cm2 on the surgical and nonsurgical side (P<0.0002), respectively. Magnitudes of areas on the surgical side, respective of the nonsurgical side, did not significantly differ between the 2 days of investigation (P>0.5). The agreement between test-retest assessments was fair to excellent on the surgical side but poor on the nonsurgical side. None of the PTPS patients experienced mirror pain. Discussion:MISD is a common finding in PTPS patients and deserves further study involving mechanism and clinical implications.

Persistent postsurgical pain after video‐assisted thoracic surgery – an observational study

The risk of persistent postsurgical pain (PPP) and subsequent pain‐related functional impairment may potentially be reduced by video‐assisted thoracic surgery (VATS) compared to thoracotomy. The aim of the study was therefore to assess in detail the incidence and consequences on activities of daily living of PPP after VATS.

Pain-related impairment of daily activities after thoracic surgery: a questionnaire validation.

Objective:Persistent postoperative pain is an acknowledged entity that reduces daily activities. Evaluation of the post-thoracotomy pain syndrome (PTPS) is often measured using traditional pain scales without in-depth questions on pain impairment. Thus, the purpose was to create a procedure-specific questionnaire for assessment of functional impairment due to PTPS. Methods:Activities were obtained from the literature supplemented by interviews with patients and surgeons. The questionnaire was validated using the Rasch model in order to describe an underlying pain impairment scale. Results:Four of 17 questions were redundant. The remaining 13 questions from low to intensive activity described functional impairment following persistent pain from thoracotomy and video-assisted thoracic surgery (VATS). No evidence for differential item functioning for gender, age or differences between open or VATS, were found. A generalized log-linear Rasch model including local dependence was constructed. Though local dependence influenced reliability, the test-retest reliability estimated under the log-linear Rasch model was high (0.88–0.96). Correlation with items from the Disability of the Arm, Shoulder and Hand (quick) questionnaire supported validity (&ggr;=0.46, P<0.0001), and procedure specificity. The analysis also procured evidence that the pain impairment questionnaire measured 2 qualitatively different pain dimensions although highly correlated (&ggr;=0.76). Conclusions:This study presents method, results and validation of a new unidimensional scale measuring procedure specific functional impairment due to PTPS following open surgery and VATS. Procedure specific tools such as this could provide important outcomes measures for future trials on persistent postsurgical pain states allowing better assessment of interventions (250).

The role of peripheral afferents in persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial of ultrasound-guided tender point blockade

BACKGROUND Severe, persistent inguinal postherniorrhaphy pain (PIPP) is a debilitating condition that develops in 2-5% of patients. PIPP may be neuropathic in nature, yet the lesion in the peripheral nervous system has not been located. Most PIPP-patients demonstrate a tender point (TP) in the medial aspect of the inguinal region that triggers pain upon minimal pressure. As TPs may play a role in the pathophysiology of PIPP, the aim of this trial was to investigate the analgesic effects of local anaesthetic TP-blockade. METHODS A randomized, double-blind, placebo-controlled, crossover trial was performed in 14 PIPP-patients and six healthy volunteers. All participated in two sessions, seven days apart, receiving 10 ml of 0.25% bupivacaine or normal saline via an ultrasound-guided fascial plane block at the TP. The TP-area was used for pain assessments (at rest, on movement, with 100 kPa pressure-algometry) and quantitative sensory testing (pressure pain thresholds, thermal detection/pain thresholds, supra-threshold heat perception), before and after the TP-blockade. RESULTS The median (95% CI) reduction in pain was 63% (44.1 to 73.6%) after bupivacaine compared with 36% (11.6 to 49.7%; P=0.003) after placebo. Significant increases in cool detection (P=0.01) and pressure pain thresholds (P=0.009) with decreases in supra-threshold heat pain perception (P=0.003) were seen after bupivacaine only. In four out of six volunteers, increased thermal and evoked-pain thresholds after bupivacaine compared with placebo, was demonstrated. CONCLUSIONS This trial demonstrates that peripheral afferent input from the TP-area is important for maintenance of spontaneous and evoked pain in PIPP. CLINICAL TRIAL REGISTRATION NCT02065219.

Late sensory changes following chest drain insertion during thoracotomy

It is well known that chest drains are associated with severe movement‐related acute pain. These noxious stimuli could play a significant role in development and maintenance of persistent post‐operative pain. Therefore we studied chest drain sites in post‐thoracotomy pain syndrome (PTPS) patients, in regard to pain and sensory dysfunction.

Quantitative sensory testing in patients with postthoracotomy pain syndrome: Part 2: variability in thermal threshold assessments.

Objectives:Quantitative sensory testing is a reference method for characterization of postsurgical neuropathic components. Correct interpretation of data requires detailed information concerning the validity of the testing methods. The objective of the study was to assess the test-retest variability of thermal thresholds in patients (n=14) with the postthoracotomy pain syndrome. Methods:Sensory mapping with a metal roller (25°C) on the surgical side delineated an area with cool sensory dysfunction. In this area and in a contralateral area, 4 prespecified sites (2.6 cm2) were outlined, in addition to the maximum pain site on the surgical side. In these total 9 sites, warmth detection threshold, cool detection threshold, and heat pain threshold were assessed. Results:Comparisons of thermal test-retest assessments did not demonstrate any significant intraside differences. The SDs of the thermal assessments in nonpain sites and in the maximum pain site ranged from 1.9 to 2.5°C and 3.5 to 6.9°C, respectively. The estimated within-patient and between-patient variances were 5% to 28% and 72% to 95%, respectively, of the total variances. Although a generally poor test-retest agreement was demonstrated, the much lower within-patient than between-patient variances facilitated estimations of highly statistical significant, within-patient differences in thermal thresholds. Discussion:In patients with postthoracotomy pain syndrome, several statistical methods indicated an excessively high variability in thermal thresholds, questioning the use of single quantitative sensory testing in assessments to characterize patients with chronic pain states.