Pharmacological Influences on the R2 Blink Reflex Response in Healthy Participants: A Systematic Review

Area of Science:

• Neuroscience
• Pharmacology
• Pain Research

Background:

• The R2 blink reflex (BR) is a brainstem response to supraorbital nerve stimulation, serving as a biomarker in pharmacological studies.
• Standard electrodes activate both tactile (R1) and nociceptive (R2) BR components, while concentric electrodes isolate the nociceptive-specific response (NBR).

Purpose of the Study:

• To systematically review and assess the pharmacological modulation of nociceptive R2 responses in healthy participants.
• To compare the effects of drugs on R2 responses measured by standard patch versus concentric electrodes.

Main Methods:

• A systematic review following PRISMA guidelines, searching PubMed, Cochrane, and Ovid for relevant studies.
• Included studies examined pharmacological interventions on R2 responses in healthy adults, extracting data on study design, drug class, electrodes, dosage, and outcomes.
• Nine studies encompassing eight drug classes met the inclusion criteria.

Main Results:

• Opioids, SSRAs, NSAIDs, and ketamine showed limited effects on R2 responses.
• Alpha-2 adrenoceptor modulators, benzodiazepines, nitrous oxide, and adenosine A1 receptor agonists demonstrated significant effects.
• The type of stimulation electrode (standard vs. concentric) did not alter the observed pharmacological modulation of R2 responses.

Conclusions:

• Nociceptive R2 components of the BR, regardless of electrode type, are comparably sensitive to pharmacological modulation.
• Findings support the use of R2 responses as a biomarker for drug effects on nociception.
• Further research is needed to distinguish local and descending modulatory system contributions to trigeminofacial circuits.