Unmet needs in the management of functional impairment in patients with chronic pain: a multinational survey.

Background: A survey of European Pain Federation 2019 attendees was conducted to identify unmet needs in chronic pain patients. Materials & methods: Four questions were asked focusing on functional impairment in chronic pain, including who are at increased risk and ways to better identify and manage these patients. Results: In total 143 respondents indicated that key issues were lack of knowledge, lack of resources/time to assess and manage chronic pain and lack of sufficient tools to identify patients at risk for functional impairment. Education and training of primary care physicians, simplified guidelines and practical tools for assessment and use of multidisciplinary teams to treat chronic pain were recommended. Conclusion: There are many unmet needs in the management of functional impairment in chronic pain patients.

Influence of lidocaine hydrochloride and penetration enhancers on the barrier function of human skin.

Skin penetration enhancers (SPEs) are commonly employed in pharmaceutical and personal care products. These compounds transiently alter the barrier properties of the skin and we have previously investigated the effects of specific SPEs on skin barrier function in vivo. In the present study the effects of incorporation of an active pharmaceutical ingredient (API), lidocaine hydrochloride (LID HCl) in the SPEs previously studied were investigated. Solutions of LID HCl were prepared and applied to the volar forearm of human subjects with occlusion for 24h. Subsequently, tape stripping and trans epidermal water loss (TEWL) measurements were conducted for treated and control sites. The activities of the desquamatory proteases, kallikrein 5 (KLK 5) and kallikrein 7 (KLK 7) and API content were also measured from the tape strips. The propylene glycol (PG) formulation increased TEWL significantly (p<0.05) compared with the other SPEs and a mixture of the SPEs. However, only the isopropyl myristate (IPM) solution altered protease activity with a significant observed increase in kallikrein 5 (KLK 5). Incorporation of LID HCl appeared to ameliorate the effects of some of the SPEs on TEWL measurements compared with our previous study. Overall uptake of LID HCl into skin from the various formulations correlated very well with changes in TEWL. The findings should have implications for the choice of SPEs in topical and transdermal formulations, particularly where the skin barrier function of patients is already impaired for example in atopic eczema or psoriasis.

Influence of skin penetration enhancers on skin barrier function and skin protease activity.

In order to overcome the skin's excellent barrier function formulation scientists often employ skin penetration enhancers (SPEs) in topical and transdermal formulations. The effects of these compounds on skin health is still not well understood at the molecular level. The aim of the present work was to probe the effects of some common SPEs on desquamatory protease activity in healthy skin. The SPEs studied were isopropyl myristate (IPM), propylene glycol, (PG), propylene glycol laurate (PGL) and Transcutol™ (TC). Occluded infinite doses of each SPE were applied to human volunteers for 24 h. Transepidermal water loss (TEWL) measurements were taken before and after application of SPEs. Tape strips were collected from the treated sites to determine protein content and the activity of two desquamatory proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7). TEWL values were also measured after tape stripping. PG was found to elevate both TEWL values and KLK7 activity to a significant extent (p<0.05). No significant effects were observed for the other SPEs. The ability of PG to alter the skin barrier at the macroscopic level and the influence of the molecule on protease activity reported here may have implications for its use in topical formulations used for the management of impaired skin barrier function such as atopic eczema or psoriasis.

Variation of stratum corneum biophysical and molecular properties with anatomic site.

Several serine protease enzymes are known to be involved in both normal desquamation and the inflammatory processes of the skin. Alteration in the activity of these proteases should also affect corneocyte maturity and size as well as stratum corneum thickness. The aim of the present work was to characterise the baseline changes in corneocyte size, corneocyte maturity, selected protease activity (specifically, Kallikreins-5 and 7, tryptase), protein content and trans-epidermal water loss (TEWL) as a function of anatomic site. The anatomic sites investigated were: cheek, abdomen, wrist and mid-ventral forearm. TEWL values were highest for the cheek (p < 0.05). The TEWL values were also significantly higher (p < 0.05) for cheek and wrist compared with other sites. Protein content was significantly lower for wrist (p < 0.05) compared with other sites. Corneocyte maturity and surface area were significantly (p < 0.05) lower for cheek and wrist compared with other sites. An excellent correlation (r (2) = 0.99) was obtained for maturity and surface area measurements. Kallikrein-5 and tryptase activity were significantly higher for the cheek compared with other sites but Kallikrein-7 values were uniform across sites. The findings have significant implications for skin permeability to drugs and other substances such as environmental toxins depending on the anatomic site of delivery or exposure.