Expression genetics identifies spinal mechanisms supporting formalin late phase behaviors

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Formalin injection in rodent hind paws is a standard pain assay.
• Nocifensive behaviors present distinct early and late phases with differing mechanisms.
• Spinal sensitization is implicated in the late phase but remains incompletely understood.

Purpose of the Study:

• To identify genes contributing to the variability in formalin-induced pain responses.
• To investigate the genetic underpinnings of the late phase of nociception.

Main Methods:

• Correlative analysis of spinal cord gene expression and formalin behavior scores across 10 mouse strains.
• Utilized a spinal cord gene expression database and expression arrays.
• Investigated Mapk8 (JNK1) gene expression and protein levels, and effects of a JNK inhibitor.

Main Results:

• Several spinal cord genes showed high correlation with late-phase formalin behavior.
• Mapk8 (JNK1) gene expression strongly correlated with behavioral responses.
• JNK1 protein levels showed an inverse relationship with mRNA.
• Selective JNK inhibition reduced late-phase licking behavior.

Conclusions:

• Inbred mouse strains exhibit significant genetic variability in pain behaviors.
• Correlating gene expression with behavior effectively identifies genes involved in pain mechanisms.
• The Mapk8 gene plays a functional role in supporting formalin-induced late-phase pain responses.