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Social agency buffers pain sensitivity during a critical window following spared nerve injury

Toddes, C. A.; Bai, K. N.; Halperin, I. E.; Keeler, W. R.; MacMillen, L. K.; Heshmati, M.; Golden, S.

2026-07-21 neuroscience
10.64898/2026.07.15.738734 bioRxiv
Show abstract

Social buffering of pain, in which social contact blunts emotional or nociceptive intensity, is well established. However, the degree to which agency over social contact, rather than general reward or social contact alone, modifies pain intensity or pain behaviors remains unclear. Using a social self-administration procedure in which mice lever-press for access to their familiar housing partner, we show that voluntary social engagement gates pain sensitivity after spared nerve injury (SNI) in male and female mice. After 8 days of training, mice regained access to social self-administration either 1 day (Early) or 5 days (Delayed) after SNI. Early access preserved pre-injury social response rates and left SNI mice indistinguishable from shams in the von Frey test of mechanical sensitivity (allodynia); Delayed access similarly preserved social response rates but failed to prevent allodynia revealing a narrow post-injury window for socially conferred pain protection. These effects were sex-dependent, with females more sensitive to both nerve injury and disruptions in social access. Further, pain buffering did not generalize to non-social reinforcers as food self-administration did not alter allodynia in SNI mice, nor did a non-contingent (forced) version of the social task reduce allodynia. Together, these findings identify a critical window in which self-directed social interaction, specifically, confers pain protection after nerve injury.

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