Dissociating pain dimensions in cold allodynia: subanesthetic ketamine reveals heritable affective-motivational traits in mice.
Pain January 29, 2026 Nicole Richter, Stefanie Schmidt, Glauce Regina Pigatto et al.
Subanesthetic ketamine reduces the affective-motivational component of pain—bites and licks—in a mouse model of oxaliplatin-induced cold allodynia, but does not affect somatosensory responses such as paw lifts and shakes and flinches. This dissociation was observed across six inbred mouse strains. The effects were transient, reversing within minutes. Ketamine plasma levels ranged from 2600 to 6200 ng/mL in males and 1300 to 3900 ng/mL in females, with significant sex differences in five strains. Hydroxynorketamine levels were higher in females, while norketamine levels showed no sex differences. These results indicate that ketamine parses cold allodynia into separate pain components, and sex-dependent metabolism influences its efficacy.