The Outpatient Prescribing Pattern of Topical Lidocaine in Al Seih

Aim: The present study aimed to describe the prescribing pattern of topical lidocaine in the outpatient setting in Al Seih. Methodology: This is a retrospective study that includes reviewing the electronic prescriptions that contained topical lidocaine among outpatients in a public hospital in Al Seih. Results: More than 52% of the patients who received topical lidocaine were males and the age of 36.84% of them was between 30 and 39 years. Most of the patients who received topical lidocaine for 7 days (64.47%). Topical lidocaine prescriptions were written mainly by residents (96.05%). More than 55% of the topical lidocaine prescriptions were prescribed by the emergency department and 38.16% of the prescriptions were prescribed by general surgery department. Conclusion: The present study showed that the prescribing of topical lidocaine was uncommon in Al Seih. Further studies are required to investigate the pattern and the frequency of topical lidocaine and other topical anesthetics in the outpatients setting and in other settings.

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.

Management issues in neuropathic pain

Neuropathic pain is a common complication to cancer and cancer treatments, such as surgery, chemotherapy, and radiation therapy. Neuropathic pain may be present in up to 40% of cancer patients and may persist independently of the cancer and affect the quality of life in disease-free cancer survivors. Particular surgery and chemotherapy may cause chronic neuropathic pain in cancer survivors. The diagnosis of neuropathic pain can be challenging and requires documentation of a nervous system lesion and pain in areas of sensory changes. The pharmacological treatment includes tricyclic antidepressants, selective serotonin–noradrenaline reuptake inhibitors (duloxetine or venlafaxine), gabapentin, and pregabalin as first-line treatments. Topical lidocaine 5%, capsaicin 8% patches, botulinum toxin type A, tramadol, and strong opioids are second- and third-line treatments. Steroids may have a role in the acute management of cancer-related neuropathic pain. Due to limited efficacy or intolerable side effects at maximal doses, combination therapy is often required and careful monitoring of effect and adverse reactions is important.

Focused ultrasound enhances the anesthetic effects of topical lidocaine in rats

Background High-intensity ultrasound has been used to induce acoustic cavitation in the skin and subsequently enhances skin permeability to deliver hydrophobic topical medications including lidocaine. In contrast, instead of changing skin permeability, pulsed application of low-intensity focused ultrasound (FUS) has shown to non-invasively and temporarily disrupt drug-plasma protein binding, thus has potential to enhance the anesthetic effects of hydrophilic lidocaine hydrochloride through unbinding it from serum/interstitial α1-acid glycoprotein (AAG). Methods FUS, operating at fundamental frequency of 500 kHz, was applied pulse-mode (55-ms pulse duration, 4-Hz pulse repetition frequency) at a spatial-peak pulse-average intensity of 5 W/cm2. In vitro equilibrium dialysis was performed to measure the unbound concentration of lidocaine (lidocaine hydrochloride) from dialysis cassettes, one located at the sonication focus and the other outside the sonication path, all immersed in phosphate-buffered saline solution containing both lidocaine (10 µg/mL) and human AAG (5 mg/mL). In subsequent animal experiments (Sprague-Dawley rats, n = 10), somatosensory evoked potential (SSEP), elicited by electrical stimulations to the unilateral hind leg, was measured under three experimental conditions—applications of FUS to the unilateral thigh area at the site of administered topical lidocaine, FUS only, and lidocaine only. Skin temperature was measured before and after sonication. Passive cavitation detection was also performed during sonication to evaluate the presence of FUS-induced cavitation. Results Sonication increased the unbound lidocaine concentration (8.7 ± 3.3 %) from the dialysis cassette, compared to that measured outside the sonication path (P < 0.001). Application of FUS alone did not alter the SSEP while administration of lidocaine reduced its P23 component (i.e., a positive peak at 23 ms latency). The FUS combined with lidocaine resulted in a further reduction of the P23 component (in a range of 21.8 − 23.4 ms after the electrical stimulations; F(2,27) = 3.2 − 4.0, P < 0.05), indicative of the enhanced anesthetic effect of the lidocaine. Administration of FUS neither induced cavitation nor altered skin conductance or temperature, suggesting that skin permeability was unaffected. Conclusions Unbinding lidocaine from the plasma proteins by exposure to non-thermal low-intensity ultrasound is attributed as the main mechanism behind the observation.