Pain sensitivity is thought to be a characteristic of each individual that affects the way a painful stimulus is perceived. In simple terms, being pain hyper- or hyposensitive results in the perception of the same stimulus as very painful or slightly painful, respectively. As a matter of fact, the same trauma results in extremely different amounts of pain reported by different individuals: extensive tissue damage is not always associated with uncontrollable pain, and minor tissue damage may be associated with excruciating pain. Therefore, something beyond tissue damage must play a role in pain perception. This “something” is frequently identified as individual pain sensitivity. While this is a sound theoretical construct, the question is what determines pain sensitivity. A naïve (but still widespread) belief is that being a constitutionally “strong” individual results in little pain sensitivity. In this context, synonyms of “strong” may be brave or resilient, among others. Accordingly, constitutionally “weak” individuals would tend to report excessive pain even with minor noxious stimuli. The implication is that the term “weak” includes a range of negative attributes that are expected to explain the excessive pain reported by these individuals.
Apparently, science has long failed to consider pain sensitivity. Today we know that pain sensitivity is the result of complex processes at different sites of the pathways that are involved in the generation, transmission, elaboration and perception of pain. Consistent with the scientific literature, I will call the processes that encode noxious stimuli as nociception, and the corresponding pathways as nociceptive pathways. The main difference between nociception and pain is that pain is a conscious process, rather than a pure neurobiological process. More information on this distinction can be found in a previous blog post ‘Can one have pain and not know it?’.
When tissue damage occurs, substances that are released in the tissue make nociceptive pathways more likely to be activated. As a result, a low intensity stimulus can generate strong pain. The nociceptive signal arrives at the spinal cord and may induce changes that increase excitability of neurons, resulting in amplification of pain. Other areas of the central nervous system involved in nociceptive transmission are activated, so that pain is now perceived at undamaged body regions, distant from the site of primary tissue damage. Psychological factors, among other variables, can lead to enhancement or attenuation of nociceptive processes, by acting both on brain circuits and through descending pathways that terminate in the spinal cord. The endogenous inhibitory system consists of a network of cells and pathways of the central nervous system and is physiologically active to attenuate pain. Its activity explains why extensive injuries are not always associated with excruciating pain, as typically observed in early stages of a trauma. However, tissue injuries can not only enhance, but also reduce the function of the inhibitory system, resulting in strong pain after modest injuries. To date, we cannot explain when and why a trauma induces enhanced or reduced function of the pain inhibitory system.
Measurements of pain sensitivity are available for human research and, partly, for clinical use. For instance, a pressure stimulus can be applied to a body region, and the subjects are asked to rate their pain intensity. In a more objective manner, a painful stimulus is applied to the foot and the withdrawal (involuntary) reflex of the leg is recorded through electromyography, providing an indication of responsiveness to the stimulus. Reference values in the pain-free population have been determined, so that it can now be ascertained whether individual patients have responses that fall outside of the “normal” range. Pain hypersensitivity has been found to be very common in chronic pain patients, a recent study revealing that 70-80% of patients attending a university pain clinic display abnormal values.
While enormous progress has been made in our understanding of pain sensitivity and its measurement, we still face a challenging question: why do different individuals have different degrees of pain sensitivity and what factors contribute to the observed individual differences despite similar trauma? We do not have a satisfactory answer to this question, partly because our tools to study the different molecular mechanisms involved in pain sensitivity in humans are extremely limited.
In summary, pain sensitivity is a complex and still poorly understood phenomenon that is not amenable to simplifications. It is profoundly affected by multiple mechanisms acting at different sites of the pathways involved in the generation and transmission of the nociceptive signal, and in the perception of pain. Hopefully, future research will provide more insight into the mechanisms underlying pain sensitivity in humans, providing a basis from which to develop more effective and individualized therapeutic strategies.
About Michele Curatolo, MD, PhD
Michele is professor of Anesthesiology and Pain Medicine at the University of Washington, Seattle, USA. I received my M.D. at the University of Messina in Italy and continued my career in Switzerland. I made my Ph.D. at the University of Aalborg in Denmark. Prior to my appointment at the University of Washington, I have been the chief of the Division of Pain Therapy and acting chair of the Department of Anesthesiology and Pain Therapy at the University of Bern, Switzerland. More details can be found at the University of Washington biosketch and LinkedIn profile.
Selection of references
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011;152:S2-15.
Curatolo M, Muller M, Ashraf A, Neziri AY, Streitberger K, Andersen OK, Arendt-Nielsen L. Pain hypersensitivity and spinal nociceptive hypersensitivity in chronic pain: prevalence and associated factors. Pain 2015;156:2373-2382.
Yarnitsky D. Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 2015;156 Suppl 1:S24-31.
Commissioning Editor: Claudia Campbell. Associate Editor: Tory Madden.