Padin, Juan-FernandoMaroto, MarcosEntrena, Jose ManuelEgea, JavierMontell, EulaliaVerges, JosepLopez, Manuela GCobos, Enrique JGarcia, Antonio G2023-05-032023-05-032022-07-31Padín JF, Maroto M, Entrena JM, Egea J, Montell E, Vergés J, et al. Synthetic Hyaluronan Disaccharide BIS014 Mitigates Neuropathic Pain in Mice. J Pain. 2023 Jan;24(1):68-83.http://hdl.handle.net/10668/22327Neuropathic pain (NP) is a challenging condition to treat, as the need for new drugs to treat NP is an unmet goal. We investigated the analgesic potential of a new sulfated disaccharide compound, named BIS014. Oral administration (p.o.) of this compound induced ameliorative effects in formalin-induced nociception and capsaicin-induced secondary mechanical hypersensitivity in mice, but also after partial sciatic nerve transection (spared nerve injury), chemotherapy (paclitaxel)-induced NP, and diabetic neuropathy induced by streptozotocin. Importantly, BIS014, at doses active on neuropathic hypersensitivity (60 mg/kg/p.o.), did not alter exploratory activity or motor coordination (in the rotarod test), unlike a standard dose of gabapentin (40 mg/kg/p.o.) which although inducing antiallodynic effects on the NP models, it also markedly decreased exploration and motor coordination. In docking and molecular dynamic simulation studies, BIS014 interacted with TRPV1, a receptor involved in pain transmission where it behaved as a partial agonist. Additionally, similar to capsaicin, BIS014 increased cytosolic Ca2+ concentration ([Ca2+]c) in neuroblastoma cells expressing TRPV1 receptors; these elevations were blocked by ruthenium red. BIS014 did not block capsaicin-elicited [Ca2+]c transients, but inhibited the increase in the firing rate of action potentials in bradykinin-sensitized dorsal root ganglion neurons stimulated with capsaicin. Perspective: We report that the oral administration of a new sulfated disaccharide compound, named BIS014, decreases neuropathic pain from diverse etiology in mice. Unlike the comparator gabapentin, BIS014 does not induce sedation. Thus, BIS014 has the potential to become a new efficacious non-sedative oral medication for the treatment of neuropathic pain.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Compound BIS014TRPV(1)analgesic drugsantiallodynic drugshyaluronan disaccharidehyaluronicneuropathic painGabapentinaMiceAnimalsCapsaicinHyaluronic AcidGabapentinTRPV Cation ChannelsNeuralgiaHyperalgesiaresearch article36087908open accessAnimalesCanales catiónicos TRPVCapsaicinaHiperalgesiaNeuralgiaRatonesÁcido hialurónico10.1016/j.jpain.2022.07.0141528-8447https://digibug.ugr.es/bitstream/10481/77916/1/1-s2.0-S1526590022003819-main.pdf