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Persistent cardiovascular and behavioral nociceptive responses to subcutaneous formalin require peripheral nerve
B K Taylor1, M A Peterson, A I Basbaum
1W. M. Keck Foundation Center for Integrative Neuroscience, University of California at San Francisco 94143, USA.
Summary
Persistent ongoing activity in peripheral nerve fibers is crucial for sustained pain responses following formalin injection. Blocking these nerve signals in the affected paw prevents prolonged pain behaviors and associated cardiovascular changes.
Area of Science:
- Neuroscience
- Pain Research
- Physiology
Background:
- The formalin test is a widely used model for studying acute and persistent pain.
- Central sensitization plays a role in persistent pain, but the contribution of peripheral nerve activity is less understood.
Purpose of the Study:
- To investigate the role of ongoing peripheral nerve inputs in Phase 2 (persistent) pain responses in the formalin test.
- To determine if peripheral nerve activity is necessary for formalin-evoked persistent pain behaviors and cardiovascular changes.
Main Methods:
- Formalin (0.625-5.0%) was injected into the rat hindpaw to induce biphasic nociceptive behaviors and cardiovascular responses (arterial pressure, heart rate).
- Local anesthesia of the hindpaw with QX-314 (2%) was performed after Phase 1 subsided but before Phase 2 began.
- Pain behaviors (flinching) and cardiovascular responses were measured.
Main Results:
- Formalin injection induced biphasic pain behaviors and cardiovascular responses, with Phase 2 responses correlating with formalin concentration.
- Local anesthesia of the formalin-injected paw with QX-314 significantly blocked Phase 2 pressor, tachycardia, and behavioral responses.
- Anesthesia of the contralateral paw did not affect Phase 2 responses, indicating a peripheral origin.
Conclusions:
- Persistent ongoing activity in peripheral afferent nerve fibers during Phase 2 is essential for the expression of persistent pain evoked by formalin.
- Peripheral nerve input is a critical determinant of sustained pain and associated cardiovascular changes in this model.