Genetic sensitivity to hot-plate nociception in DBA/2J and C57BL/6J inbred mouse strains: Possible sex-specific mediation by δ2-opioid receptors

Jeffrey S. Mogil, Susan P. Richards, Laurie A. O'Toole, Melinda L. Helms, Steve R. Mitchell, John K. Belknap

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


The inbred mouse strains, DBA/2J (D2) and C57BL/6J (B6), display differential sensitivity to acute, thermal nociception as measured on the hot-plate (HP) assay. In an ongoing quantitative trait locus (QTL) mapping study designed to reveal genomic loci showing genetic linkage to HP sensitivity, a putative QTL on chromosome 4 (50-80 cM from the centromere) has been identified that appears to account for variability in this trait in male, but not female mice. An obvious candidate gene located in this same chromosomal region is Oprd1, which encodes the murine δ-opioid receptor. In an attempt to evaluate whether Oprd1 represents this sex-specific QTL for HP sensitivity, we tested D2 and B6 mice of both sexes for HP latencies (hindpaw-lift, -lick or -flutter) following systemic injections of saline, or the opioid receptor antagonists naloxone (NAL; 0.1 and 10 mg/kg), nor-binaltorphimine (nor-BNI; 5 mg/kg), naltrindole (NTI; 5 mg/kg), 7-benzylidenenaltrexone (BNTX; 0.7 mg/kg), or naltriben (NTB; 1 mg/kg). High-dose (10 mg/kg) NAL lowered HP latencies in D2, but not B6 mice, suggesting that the higher HP latencies exhibited by D2 mice reflect opioid mechanisms. HP latencies in both strains and both sexes were unaffected by pretreatment with low-dose (0.1 mg/kg) NAL or nor-BNI, suggesting that neither μ nor κ receptors affect basal nociceptive sensitivity. The δ-receptor antagonist, NTI, and the δ2-specific antagonist, NTB, (but not the δ1-specific antagonist, BNTX) effectively lowered HP latencies in a strain- and sex-dependent manner: D2 male > B6 male > D2 female > B6 female. These data support the possibility that Oprd1 is a QTL mediating HP sensitivity in mice, and more generally illustrate the important roles of genetic background and gender in the perception of pain.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
Issue number2-3
StatePublished - Apr 1997


  • QTL mapping
  • opiate
  • pain sensitivity
  • sex differences
  • strain differences

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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