Accepted

Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose capsaicin. Release properties were measured in Franz diffusion cell and continuous flow-through cell approaches. Capsaicin was detected with HPLC-UV and UV spectrophotometry. Raman spectroscopy was conducted on human skin samples exposed to the TTS. A surgical incision or carrageenan injection was performed on one hind paw of male Wistar rats. TTSs were applied to the epilated dorsal skin. Patches were kept on the animals for 6 h. The thermal hyperalgesia and mechanical pain threshold of the hind paws were detected. Patches exhibited controlled, zero-order kinetic capsaicin release. According to the Raman mapping, capsaicin penetrated into the epidermis and dermis of human skin, where the target receptors are expressed. The thermal pain threshold drop of the operated rat paws was reversed by capsaicin treatment compared to that of animals treated with control patches. It was concluded that our modified silicone-polymer-based capsaicin-containing TTS is suitable for the relief of traumatic and inflammatory pain.

Transient receptor potential vanilloid 1 (TRPV1) agonists that bind to the vanilloid pocket are being actively studied in the pharmaceutical industry to develop novel treatments for chronic pain and cancer. To discover synthetic vanilloids without the side effect of capsaicin, a time-consuming process of drug candidate selection is essential to a myriad of chemical compounds. Herein, we propose a novel approach to field-effect transistors for the fast and facile screening of lead vanilloid compounds for the development of TRPV1-targeting medications. The graphene field-effect transistor was fabricated with human TRPV1 receptor protein as the bioprobe, and various analyses (SEM, Raman, and FT-IR) were utilized to verify successful manufacture. Simulations of TRPV1 with capsaicin, olvanil, and arvanil were conducted using AutoDock Vina/PyMOL to confirm the binding affinity. The interaction of the ligands with TRPV1 was detected via the fabricated platform, and the collected responses corresponded to the simulation analysis.

The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by severe joint pain. There are conflicting results for the association of Interleukin 4 (IL4) variable number tandem repeats (VNTR; rs8179190) polymorphism with RA. Therefore, we performed a meta-analysis of the available studies to investigate the association of IL4 VNTR polymorphism with RA risk and severity in the overall populations and Asian, Egyptian, European, and Turkish ethnicities by sub-group analyses. Eight studies involving 1993 RA patients and 1732 controls were included in this meta-analysis. We found increased RA risk for the susceptible "R2R2" genotype and "R2" allele under heterozygous, recessive, and allelic models in the Asian populations (p < 0.00001, p < 0.0001, p = 0.001). We observed a significant association between "R2R2" genotype and "R2" allele for RA protection in the Turkish population under heterozygous, recessive, and allelic models (p = 0.01, p = 0.004, p = 0.002). Disease severity-based analysis revealed significant association for "R2R2" genotype and "R2" allele with RA severity under homozygous, heterozygous, recessive, dominant, and allelic models(p = 0.0004, p = 0.03, p = 0.02, p = 0.003, p = 0.01), specifically in Asian populations (p = 0.009, p = 0.02, p = 0.003, p = 0.03, p = 0.01) and under heterozygous, dominant, and allelic genetic models in Egyptian (p = 0.0001, p < 0.0001, p < 0.0001) and European (p = 0.002, p = 0.0007, p = 0.0006) populations. In silico analysis suggested that the susceptible "R2" allele changes the RNA secondary structure to a stable form by changing minimum free energy(ΔG) from – 115.20 to – 136.40 kcal/mol, which might lead to increased stability of IL-4 in RA patients. Overall, the meta-analysis suggests for the involvement of susceptible "R2" allele with RA risk in the Asian populations, RA severity in the overall populations (specifically in Asian, Egyptian, & European populations), and RA protection in the Turkish population.

Metastatic spread of prostate cancer to the skeleton may result in debilitating bone pain. In this review, we address mechanisms underpinning the pathobiology of metastatic prostate cancer induced bone pain (PCIBP) that include sensitization and sprouting of primary afferent sensory nerve fibres in bone. We also review current treatments and pain responses evoked by various treatment modalities in clinical trials in this patient population.

Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management.

To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis.