Keratinocyte Biomarkers Distinguish Painful Diabetic Peripheral Neuropathy Patients and Correlate With Topical Lidocaine Responsiveness

This study investigated quantifiable measures of cutaneous innervation and algesic keratinocyte biomarkers to determine correlations with clinical measures of patient pain perception, with the intent to better discriminate between diabetic patients with painful diabetic peripheral neuropathy (PDPN) compared to patients with low-pain diabetic peripheral neuropathy (lpDPN) or healthy control subjects. A secondary objective was to determine if topical treatment with a 5% lidocaine patch resulted in correlative changes among the quantifiable biomarkers and clinical measures of pain perception, indicative of potential PDPN pain relief. This open-label proof-of-principle clinical research study consisted of a pre-treatment skin biopsy, a 4-week topical 5% lidocaine patch treatment regimen for all patients and controls, and a post-treatment skin biopsy. Clinical measures of pain and functional interference were used to monitor patient symptoms and response for correlation with quantitative skin biopsy biomarkers of innervation (PGP9.5 and CGRP), and epidermal keratinocyte biomarkers (Nav1.6, Nav1.7, CGRP). Importantly, comparable significant losses of epidermal neural innervation (intraepidermal nerve fibers; IENF) and dermal innervation were observed among PDPN and lpDPN patients compared with control subjects, indicating that innervation loss alone may not be the driver of pain in diabetic neuropathy. In pre-treatment biopsies, keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling were all significantly increased among PDPN patients compared with control subjects. Importantly, no keratinocyte biomarkers were significantly increased among the lpDPN group compared with control. In post-treatment biopsies, the keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling intensities were no longer different between control, lpDPN, or PDPN cohorts, indicating that lidocaine treatment modified the PDPN-related keratinocyte increases. Analysis of the PDPN responder population demonstrated that increased pretreatment keratinocyte biomarker immunolabeling for Nav1.6, Nav1.7, and CGRP correlated with positive outcomes to topical lidocaine treatment. Epidermal keratinocytes modulate the signaling of IENF, and several analgesic and algesic signaling systems have been identified. These results further implicate epidermal signaling mechanisms as modulators of neuropathic pain conditions, highlight a novel potential mode of action for topical treatments, and demonstrate the utility of comprehensive skin biopsy evaluation to identify novel biomarkers in clinical pain studies.

EP.FRI.309 Rib fractures – an overlooked part of general surgical take? An audit and creation of a local pathway

Introduction Battle et al devised a validated scoring system to stratify patients with rib fractures (RF) at risk of complications based on age; number of fractures; oxygenation; respiratory illness and anticoagulation use. Risk of complications increases with score e.g. ≤10 and ≥31 give estimated complications risk of 13% and 88% respectively (2). Method We conducted a local retrospective audit of 45 patients admitted with RF over 26 months. Initial and subsequent analgesia was recorded. Four subgroups were created based on Batlle score: ≤10, 11-20, 21-30, ≥31. Outcomes included complications, length of stay (LOS) and mortality. Results Whilst overall median score was 18, we observed 20% (n = 9) scored ≥31. Initially, oral analgesia alone was given to 64% of patients; 66% went on to require lidocaine patch and 15% required patient controlled analgesia. Only 2.2% (n = 1) received regional analgesia. Despite 35.6% (n = 16) scoring ≥21, only four proactive critical care referrals were made. Overall pneumonia rate was 20% (n = 9); 44% (n = 4) in the ≥31 group. There were two deaths overall, both in the ≥31 group. Median LOS was 3 days; however 44% (n = 4) of the ≥31 group required ≥7 days. Conclusion One in five RF cases scored ≥31 and consequently had the worst outcomes. There was initial suboptimal analgesia, inadequate early escalation of higher risk patients to critical care and low rates of regional blocks. Consequently, we have created a local pathway based on Battle score (2) to standardise risk stratification and management of these patients in order to improve outcomes.

A randomized clinical trial on the effect of a lidocaine patch on shoulder pain relief in laparoscopic cholecystectomy

The incidence of laparoscopy-related shoulder pain reaches 90% in women. We evaluated the effect of lidocaine patch 5% on the shoulder pain after laparoscopic cholecystectomy (LC) in female patients. Total 63 female patients were randomly allocated to patch group (n = 31) and control group (n = 32). Patch group received lidocaine patch 5% and dressing retention tape on both shoulder, and control group received only dressing retention tape. Abdominal and shoulder pains were evaluated with rating on numeric rating scale (0 = no pain and 10 = the worst pain) at baseline and at 30 min, 6 h, 24 h, and 48 h after surgery. There were no significant differences in patient characteristics and operation details. The overall incidence of shoulder pain was significantly lower in patch group than in control group (42% vs. 78%, P = 0.005). The severity of shoulder pain also was significantly reduced in patch group compared to control group at 24 h and 48 h after surgery (P = 0.01 and P = 0.015, respectively). Complications related to lidocaine patch were not found except nausea. Lidocaine patch 5% reduced the incidence and severity of postoperative shoulder pain in female patients undergoing LC without complications.

Topical 5% lidocaine patches for treating postherpetic neuralgia: a survey among nurses and patients

Introduction: Postherpetic neuralgia (PHN) is associated with moderate to severe pain with peripheral and central mechanisms. While there is no clear-cut first-line therapeutic approach to PHN pain control, lidocaine patches are frequently used as monotherapy or part of a multimodal pain regimen. Methods: An online survey, the first of its kind, was conducted among PHN patients (n = 153) and nurses (n = 151) in order to determine clinical and patient knowledge, attitudes and practices toward the lidocaine patch and current unmet needs. Results: Results of the survey indicated that PHN patients are prescribed a mean of 2.6 medications to control their PHN pain, including the lidocaine patch. There were negative responses related to the patches’ ability to adhere to the skin. Patients reported the use of tape to hold the patches in place and/or patches that detached completely, truncating the therapeutic dose period. Most nurses (53%) found the biggest obstacle to PHN pain control was noncompliance and 98% stated that reliable patch adhesion for the intended 12-hour application was “somewhat important” or “very important” for PHN pain control. Forty-five percent of nurses said that poor patient adherence to PHN analgesic regimens was related to poor adhesion of the lidocaine patch. Conclusion: A new bioequivalent lidocaine patch has been developed with better adhesive characteristics, nine-fold greater bioavailability, and improved form factor.