Sigma-1 receptor antagonism restores injury-induced decrease of voltage-gated Ca2+ current in sensory neurons.

Area of Science:

• Neuroscience
• Molecular Biology
• Pain Research

Background:

• Sigma-1 receptor (σ1R) is an endoplasmic reticulum chaperone protein involved in modulating pain responses.
• Peripheral nerve injury can lead to sensory dysfunction, partly due to altered voltage-gated calcium channel (VGCC) activity.
• Previous work indicated inhibited voltage-gated calcium current in sensory neurons post-axotomy.

Purpose of the Study:

• To investigate the role of σ1R in sensory neuron dysfunction following peripheral nerve injury.
• To determine if σ1R activation affects voltage-gated calcium channel (VGCC) function in injured sensory neurons.

Main Methods:

• Electrophysiological recordings were performed on dissociated rat dorsal root ganglion (DRG) neurons.
• Neurons were obtained from control (skin incision) and spinal nerve ligation (SNL) groups.
• The effects of σ1R agonists (PTZ, DTG) and antagonists (BD1063, BD1047) on calcium current (ICa) were assessed.

Main Results:

• σ1R agonists (PTZ, DTG) dose-dependently inhibited ICa in both control and axotomized (SNL L5) DRG neurons.
• These agonists shifted VGCC activation and inactivation curves leftward and accelerated inactivation.
• The σ1R antagonist BD1063 increased ICa specifically in injured (SNL L5) neurons, but not in control neurons.

Conclusions:

• Activation of σ1R leads to decreased ICa in sensory neurons.
• These findings suggest that σ1R plays a significant role in the generation of pain following peripheral nerve injury.