Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with...

Area of Science:

• Neuroscience
• Pain Research
• Cellular Electrophysiology

Background:

• Ongoing pain is associated with ongoing activity (OA) in human C-fiber nociceptors.
• Rodent pain models often focus on allodynia and Aβ fibers, not C-fiber nociceptors or ongoing pain.
• Mechanisms generating nociceptor OA and ongoing pain remain poorly understood.

Purpose of the Study:

• To define neurophysiological alterations underlying nociceptor OA.
• To investigate mechanisms of OA generation in C-fiber nociceptors.
• To explore the role of serotonin and depolarization in promoting OA.

Main Methods:

• Isolated dorsal root ganglion neurons from animals with and without spinal cord injury.
• Novel automated algorithms for analyzing membrane potential fluctuations.
• Electrophysiological recordings to assess resting membrane potential, action potential threshold, and spontaneous activity.

Main Results:

• Spinal cord injury induced three OA-promoting alterations in probable nociceptors: prolonged depolarization, hyperpolarized action potential threshold, and increased large depolarizing spontaneous fluctuations (DSFs).
• Serotonin alone lowered action potential threshold in neurons from uninjured animals.
• Serotonin combined with depolarization potentiated DSFs and OA, modeling inflammation.

Conclusions:

• Nociceptors possess intrinsic specializations for generating OA.
• These OA-generating mechanisms may contribute to both chronic and acute pain conditions.
• Findings highlight potential therapeutic targets for ongoing pain.