J Neurogastroenterol Motil.  2016 Jan;22(1):129-140. 10.5056/jnm15091.

Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channels in Primary Sensory Neurons in Rats with Diabetes

• Hu J
• Song ZY
• Zhang HH
• Qin X
• Hu S
• Jiang X
• Xu GY

• KMID: 2379712
• DOI: http://doi.org/10.5056/jnm15091

Abstract

BACKGROUND/AIMS
Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes.
METHODS
Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs.
RESULTS
STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats.
CONCLUSIONS
Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.

Keyword

Colonic hypersensitivity; Diabetes; Dorsal root ganglion; Voltage-gated sodium channels

MeSH Terms

Abdominal Pain
Action Potentials
Adult
Animals
Architectural Accessibility
Blotting, Western
Citric Acid
Colon*
Diagnosis-Related Groups
Female
Ganglia, Spinal
Humans
Hypersensitivity*
Injections, Intraperitoneal
Membrane Potentials
Neurons
Rats*
Sensory Receptor Cells*
Sodium
Sodium Channels
Streptozocin
Up-Regulation
Voltage-Gated Sodium Channels*
Citric Acid
Sodium
Sodium Channels
Streptozocin
Voltage-Gated Sodium Channels