RT Journal Article
T1 Small Synthetic Hyaluronan Disaccharide BIS014 Mitigates Neuropathic Pain in Mice.
A1 Padin, Juan-Fernando
A1 Maroto, Marcos
A1 Entrena, Jose Manuel
A1 Egea, Javier
A1 Montell, Eulalia
A1 Verges, Josep
A1 Lopez, Manuela G
A1 Cobos, Enrique J
A1 Garcia, Antonio G
K1 Compound BIS014
K1 TRPV(1)
K1 analgesic drugs
K1 antiallodynic drugs
K1 hyaluronan disaccharide
K1 hyaluronic
K1 neuropathic pain
K1 Gabapentina
AB Neuropathic 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.
PB Churchill Livingstone
YR 2022
FD 2022-07-31
LK http://hdl.handle.net/10668/22327
UL http://hdl.handle.net/10668/22327
LA en
NO Padín 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.
DS RISalud
RD Apr 19, 2025