Our results show that pain tolerance positively predicts social network size. This therefore supports our hypothesis that variation in the μ-opioid system underlies individual differences in sociality. These results are consistent with a recent PET imaging experiment demonstrating a correlation between μ-opioid receptor availability and attachment style, such that individuals showing greater avoidance of social attachment exhibit lower receptor densities15. Our findings are also in agreement with previous pain tolerance studies indirectly implicating the endogenous opioid system in human social bonding activities such as music-making18, dancing19 and laughter20. In addition, laughter has since been shown to correlate with elevated μ-opioid activity, as measured by PET scanning (Manninen et al. in prep). This suggests that tests of pain tolerance like that used in our study may indeed serve as a useful proxy for assessing activation of the μ-opioid system.

Variation in μ-opioid receptor signalling may be due to underlying differences in both endogenous opioid release and receptor density, though their relative contribution is yet to be fully determined. However, studies of oxytocin and vasopressin signalling in rodents have shown that CNS receptor densities strongly modulate the influence of these neuropeptides, irrespective of neuropeptide abundance21. In fact, analyses of post-mortem brain tissue and in vivo PET studies in humans have revealed a broad range of μ-opioid receptor densities within the population, differing by at least 30–50%22. Such variation is likely to considerably affect the potency of β-endorphin11. Genetic studies suggest these differences in receptor density are partly the result of a non-synonymous single-nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), substituting aspartic acid for asparagine (A118G)23. This functional polymorphism is relatively common in the population, with the minor G allele having a frequency of 10–30%24 and is associated with reduced μ-opioid receptor expression24,25. The G allele has also been linked to increased social withdrawal26 and reactivity to social rejection27, as well as greater pain sensitivity and reduced relief from opiate drugs28. This is therefore in line with our proposition that variation in the μ-opioid system contributes to individual differences in both social behaviour and pain tolerance.

We acknowledge that use of pain tolerance as a proxy for μ-opioid receptor signalling, rather than its direct measurement, represents a limitation of our research. However, the μ-opioid system is critically involved in pain modulation6,29 and numerous PET studies implicate μ-opioidergic activation in both experimental and clinical pain settings30. Most notably, in humans undergoing a sustained muscular pain challenge, individuals exhibiting higher activity of the μ-opioid system report reduced sensory and affective pain31. A possible future direction that would benefit research in this field would be to combine PET scanning with a range of different pain tests to determine how reliably they can predict activity of the μ-opioid system. We also recognise the possible involvement of non-opioid signalling pathways, especially given the complex neurochemistry underlying pain responses32,33. In particular, oxytocin, vasopressin and endocannabinoids are all implicated in social behaviour34,35, as well as having analgesic effects36,37,38. Indeed, it is likely that they act in concert with β-endorphin39,40,41.

Further research is required to understand the causality of this relationship between pain tolerance and network size. It may be that individuals with genetic variants conferring enhanced μ-opioid neurotransmission derive greater reward from social interactions, thereby seeking more company. An alternative, though not mutually exclusive, explanation is that individuals leading lives rich in social interactions may release higher levels of endogenous opioids and/or have elevated receptor expression. However, we currently lack knowledge regarding the neuroplasticity exhibited by the μ-opioid system. This is of particular interest in relation to psychiatric disorders. Indeed, healthy females asked to sustain a sad mood for only 30 minutes show a reduction in μ-opioid receptor activation42. Thus prolonged sadness, as experienced by those suffering from depression, may over time lead to a significant fall in opioidergic signalling. We hypothesise that reduced μ-opioid activity may characterise the onset of conditions such as depression and schizophrenia, resulting in the common symptoms of anhedonia and social withdrawal. Indeed, endogenous opioids mediate hedonic experiences and are integral to our feelings of social connection8,12. In support of this, there is evidence of compromised μ-opioid receptor signalling in patients suffering from depression and schizophrenia43,44 and studies using rodent models of depression also implicate the μ-opioid system45.

With respect to the other notable results of our analysis, fitness was primarily included in the regression model to account for its influence on pain tolerance but revealed an interesting and novel negative relationship with network size. This indicates a trade-off between leading a socially active versus a physically active life. Beyond the obvious constraint of time, this relationship may reflect our underlying neurobiology such that individuals who exercise more may have greater reliance on this method of promoting β-endorphin release, rather than through social interactions. Though exercise is frequently prescribed as a treatment for depression, perhaps focus should also be placed on strengthening and expanding an individual’s social ties.

The relationship reported here between stress and network size may reflect the beneficial effects of social support in dealing with stressful situations46, since measures of social support often correlate with social network size47. Interestingly, one study found that the number of Facebook friends (a known correlate of real-world social network size48) is associated with enhanced perceptions of social support and reduced stress49. Whether online social networks play a role in relieving stress (or even intensifying it) over and above an individual’s actual social interactions remains uncertain. However, an alternative interpretation of our data is that stressed individuals find less time for social engagement and thus their network decreases in size.

Understanding the biological causes of variation in social network size is of particular interest given the robust association between an individual’s social support and their health, ranging from functioning of their immune, endocrine and cardiovascular systems46 to myelin integrity50. Interestingly, it is an individual’s perceived level of social support that may often be a more reliable indicator of their health status46,51. Compared to other lifestyle factors, we have limited understanding of the mechanisms via which sociality influences morbidity and mortality risk52, though reduced activation of the neuroendocrine stress response likely plays a significant role in both humans51,53 and animals54. Since β-endorphin is known to alleviate the stress response55 and protect against inflammation and cancer56, the activity of an individual’s endogenous μ-opioid system may have important consequences for their health. However, such a direct interaction between social and somatic health is yet to be explored.

In summary, there is substantial evidence that μ-opioid neurotransmission influences sensitivity not only to our physical environment but also our social one. This study adds to previous research implicating the μ-opioid system as a key neural substrate upon which human sociality has evolved. A better understanding of the neurobiological mechanisms underpinning our social lives is imperative, especially since our technology-driven world is rapidly changing the nature of social relationships and certainly outpacing any biological adaptations. Sociality is clearly of adaptive value to our species, yet in this digital era deficiencies in our social interactions may be one of the overlooked factors contributing to the declining health of our modern society.