TY - JOUR
T1 - Possible involvement of peripheral TRP channels in the hydrogen sulfide-induced hyperalgesia in diabetic rats 11 Medical and Health Sciences 1109 Neurosciences
AU - Roa-Coria, José Eduardo
AU - Pineda-Farias, Jorge Baruch
AU - Barragán-Iglesias, Paulino
AU - Quiñonez-Bastidas, Geovanna Nallely
AU - Zúñiga-Romero, Ángel
AU - Huerta-Cruz, Juan Carlos
AU - Reyes-García, Juan Gerardo
AU - Flores-Murrieta, Francisco Javier
AU - Granados-Soto, Vinicio
AU - Rocha-González, Héctor Isaac
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/1/3
Y1 - 2019/1/3
N2 - Background: Peripheral diabetic neuropathy can be painful and its symptoms include hyperalgesia, allodynia and spontaneous pain. Hydrogen sulfide (H 2 S) is involved in diabetes-induced hyperalgesia and allodynia. However, the molecular target through which H 2 S induces hyperalgesia in diabetic animals is unclear. The aim of this study was to determine the possible involvement of transient receptor potential (TRP) channels in H 2 S-induced hyperalgesia in diabetic rats. Results: Streptozotocin (STZ) injection produced hyperglycemia in rats. Intraplantar injection of NaHS (an exogenous donor of H 2 S, 3-100 μg/paw) induced hyperalgesia, in a time-dependent manner, in formalin-treated diabetic rats. NaHS-induced hyperalgesia was partially prevented by local intraplantar injection of capsazepine (0.3-3 μg/paw), HC-030031 (100-316 μg/paw) and SKF-96365 (10-30 μg/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3-30 μg/paw), HC-030031 (100-1000 μg/paw) and SKF-96365 (10-100 μg/paw) reduced formalin-induced nociception in diabetic rats. Contralateral injection of the highest doses used did not modify formalin-induced flinching behavior. Hyperglycemia, at 21 days, also increased protein expression of cystathionine-β-synthase enzyme (CBS) and TRPC6, but not TRPA1 nor TRPV1, channels in dorsal root ganglia (DRG). Repeated injection of NaHS enhanced CBS and TRPC6 expression, but hydroxylamine (HA) prevented the STZ-induced increase of CBS protein. In addition, daily administration of SKF-96365 diminished TRPC6 protein expression, whereas NaHS partially prevented the decrease of SKF-96365-induced TRPC6 expression. Concordantly, daily intraplantar injection of NaHS enhanced, and HA prevented STZ-induced intraepidermal fiber loss, respectively. CBS was expressed in small- and medium-sized cells of DRG and co-localized with TRPV1, TRPA1 and TRPC6 in IB4-positive neurons. Conclusions: Our data suggest that H 2 S leads to hyperalgesia in diabetic rats through activation of TRPV1, TRPA1 and TRPC channels and, subsequent intraepidermal fibers loss. CBS enzyme inhibitors or TRP-channel blockers could be useful for treatment of painful diabetic neuropathy.
AB - Background: Peripheral diabetic neuropathy can be painful and its symptoms include hyperalgesia, allodynia and spontaneous pain. Hydrogen sulfide (H 2 S) is involved in diabetes-induced hyperalgesia and allodynia. However, the molecular target through which H 2 S induces hyperalgesia in diabetic animals is unclear. The aim of this study was to determine the possible involvement of transient receptor potential (TRP) channels in H 2 S-induced hyperalgesia in diabetic rats. Results: Streptozotocin (STZ) injection produced hyperglycemia in rats. Intraplantar injection of NaHS (an exogenous donor of H 2 S, 3-100 μg/paw) induced hyperalgesia, in a time-dependent manner, in formalin-treated diabetic rats. NaHS-induced hyperalgesia was partially prevented by local intraplantar injection of capsazepine (0.3-3 μg/paw), HC-030031 (100-316 μg/paw) and SKF-96365 (10-30 μg/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3-30 μg/paw), HC-030031 (100-1000 μg/paw) and SKF-96365 (10-100 μg/paw) reduced formalin-induced nociception in diabetic rats. Contralateral injection of the highest doses used did not modify formalin-induced flinching behavior. Hyperglycemia, at 21 days, also increased protein expression of cystathionine-β-synthase enzyme (CBS) and TRPC6, but not TRPA1 nor TRPV1, channels in dorsal root ganglia (DRG). Repeated injection of NaHS enhanced CBS and TRPC6 expression, but hydroxylamine (HA) prevented the STZ-induced increase of CBS protein. In addition, daily administration of SKF-96365 diminished TRPC6 protein expression, whereas NaHS partially prevented the decrease of SKF-96365-induced TRPC6 expression. Concordantly, daily intraplantar injection of NaHS enhanced, and HA prevented STZ-induced intraepidermal fiber loss, respectively. CBS was expressed in small- and medium-sized cells of DRG and co-localized with TRPV1, TRPA1 and TRPC6 in IB4-positive neurons. Conclusions: Our data suggest that H 2 S leads to hyperalgesia in diabetic rats through activation of TRPV1, TRPA1 and TRPC channels and, subsequent intraepidermal fibers loss. CBS enzyme inhibitors or TRP-channel blockers could be useful for treatment of painful diabetic neuropathy.
KW - Cystathionine-β-synthase
KW - Hydrogen sulfide
KW - Hyperalgesia
KW - Painful diabetic peripheral neuropathy
KW - Streptozotocin-induced diabetes
KW - Transient receptor potential channels
UR - http://www.scopus.com/inward/record.url?scp=85059379620&partnerID=8YFLogxK
U2 - 10.1186/s12868-018-0483-3
DO - 10.1186/s12868-018-0483-3
M3 - Artículo
C2 - 30602386
AN - SCOPUS:85059379620
SN - 1471-2202
VL - 20
JO - BMC Neuroscience
JF - BMC Neuroscience
IS - 1
M1 - 1
ER -
