Social variables affect phenotype in the neuroma model of neuropathic pain

Abstract

When the degree of genetic determination of a trait (i.e. its heritability) is high, one tends to presume that environmental factors will not modify its expression by much. Contrary to this expectation, we show here in rats that a psychosocial-behavioral variable, the identity of cagemates, can largely over-ride genetic predisposition to pain behavior. We used selection-line rats that consistently show high (HA) or low (LA) pain phenotype (autotomy) in the neuroma model of neuropathic pain. Normally, HA animals show autotomy after nerve injury while LA animals do not. However, when caged together with HA rats, LA rats showed high levels of autotomy. This occurred even when the individual HA cagemates were familiar preoperatively, and it did not depend on the actual performance of autotomy by the HA rats. Indeed, cage bedding soiled by HA rats was sufficient to induce a modest level of autotomy in LA animals. Chemical cues associated with HA rats, perhaps in combination with behavioral characteristics, are apparently able to induce pain phenotype despite the powerful protection otherwise rendered by the LA genotype. Social factors must be considered in behavior-related research on rodents that have undergone genetic modification. More generally, the overwhelming influence that psychosocial-behavioral variables have on pain perception, and on pain behavior, in humans may have evolutionary roots deeper than has previously been appreciated.