I am a final year PhD student in Professor Stephen ‘Mac’ McMahon’s laboratory at the Wolfson Centre for Age-Related Diseases, King’s College London. Sadly, Mac recently passed away, and I feel incredibly privileged to have been able to work with him for the past six years. I am pleased to have the opportunity to talk about one of our collaborative research projects.
Broadly, the focus of my PhD research has been on pain mechanisms in humans, and I use psychophysical testing, which is studying the relationship between physical sensation and our own judgement of sensory experiences. I specifically use quantitative sensory testing (QST), to measure my participants’ perception to different types of painful and non-painful sensations. One of the QST techniques I use is a highly standardised protocol that was developed by the German Research Network on Neuropathic Pain (DFNS).
During testing, the participant is presented with different types of precisely calibrated mechanical and thermal sensations, such as vibration stimulation and gentle heating. In this way, I can generate a sensory sensitivity profile of that person and compare that with data from other participants. In this blog, I will be discussing our recently published study on pain sensitivity as a biological marker for self-harm in young people, where we used DFNS QST to estimate the sensory sensitivity of young people with and without self-harm.
Suicide remains a major public health concern and is the second leading cause of death in young people. According to the World Health Organisation, approximately 800,000 people die by suicide every year, and it is among the top twenty leading causes of death worldwide. Identification of ‘risk and protective factors’ has been highlighted as critical to the prevention of suicide, but as yet, and despite decades of research, none have been identified that could be applied clinically with confidence. Self-harm necessitating hospital treatment is considered the strongest known predictor of suicide.
Interpersonal-psychological theories of suicidal behaviour propose that people who engage in suicidal behaviour must develop an acquired capability to do so “through a process of repeatedly experiencing painful and otherwise provocative events”. Within this framework, repeated self-harm is one mechanism by which individuals may habituate themselves to the experience of pain and strengthen opponent processes, whereby initial fear and pain is replaced by relief and analgesia. This may lead to at-risk individuals overcoming the instinct for self-preservation and attempting lethal self-injury.
There is some evidence that reduced sensitivity to painful sensations is a feature of people with self-harm, and much of the evidence for this comes from studies in adults with borderline personality disorder (BPD). While it is unclear whether reduced pain sensitivity arises as a consequence of repeated self-harm, is an effect of psychiatric comorbidity, or whether pain sensitivity changes are present prior to the onset of self-harm, we questioned whether pain sensitivity could be used to identify individuals at-risk of repeated self-harm and suicide. To investigate this, we studied a particularly high-risk group for self-harm and suicide: young people living in local authority-run group homes and foster care. These young people had been removed from the family home due to experience of abuse and neglect, and although looked-after young people only make up less than 1% of the UK’s under-18s, they account for about half of all completed suicides.
Using DFNS QST, we showed that young people living in care with and without self-harm have significantly reduced sensitivity to a wide range of painful sensations compared to age and gender matched young people living at home and, surprisingly, this reduced sensitivity was also evident in response to a range of non-painful sensations. In almost all instances, we saw that reduced sensitivity increased with the incidence and frequency of self-harm within the previous year. The young people in our sample living in care with no self-harm also had reduced sensitivity compared to young people living at home; this suggests that these sensory changes may be present prior to the onset of self-harm and are a consequence of adverse childhood experiences. The extent of these sensory differences across our sample was surprising, and to our knowledge this is the first study to report this in response to such a broad range of sensations. So how do we account for these differences in sensory sensitivity?
What is pain?
Pain is a highly adaptive and salient sensory experience, but we also have an innate ability to modulate our experience of pain. This capacity for pain modulation enables us to ignore injury and escape danger, and also explains why sometimes pain can feel good, like the ‘runners high’ or eating very spicy food. But taking these examples, motivation and the context within which pain is experienced is very important! Anxious feelings, grief or being in a bad mood can make pain feel much worse.
Tissue damage, or threats to our body, activates specialised sensory nerve fibres called nociceptors. Nociceptor activity is sent into the spinal cord for initial processing in the dorsal horn region. The output from the spinal dorsal horn is transmitted to the brain, where pain-related activity is processed in multiple brain regions, including the thalamus, the somatosensory cortex and the amygdala. The processing in these areas together results in what we feel as pain. It is a multidimensional experience with sensory, cognitive and emotional components.
This can be described as ‘bottom-up’ processing. However, processing in the brain can result in descending neural activity which feeds back to the dorsal horn of the spinal cord, where incoming nociceptive information can be modulated in a positive or negative direction. This is called ‘top-down’ processing. Many circumstances, for instance, physical activity or positive mood, can activate these descending controls to reduce sensory inputs, and this is called descending inhibition.
Conversely, chronic pain or negative affect can amplify sensory inputs and augment the experience of pain, and this is called descending facilitation. We are still trying to understand how descending perceptual signals influence spinal neuronal activity, but it is clear that our past experiences, expectations, attention and emotions profoundly influence how we perceive current pain.
In this video, Mac and I demonstrated a psychophysical experiment called conditioned pain modulation for the BBC, which is designed to measure descending pain inhibition (from 38–43 mins).
There are many reasons why people self-harm, and two cited examples are to regulate emotions and reduce dissociative symptoms. In this context, physical pain is used to modulate affective arousal, and the findings from our study suggests one of the outcomes of this is an enhancement of descending pain inhibition. This provides a potential mechanistic basis for the sensory hyposensitivity we observed and supports the interpersonal-psychological theories of suicidal behaviour, i.e., habituation to pain and strengthening of opponent processes. Therefore, at-risk individuals habituated to pain may be more likely to frequently self-harm and attempt suicide. We concluded from our results that pain sensitivity is a biomarker for incidence and frequency of self-harm in young people, and that a simple, clinical measure of pain sensitivity (pressure pain threshold) could be used for assessment of risk of self-harm in young people. Leading on from this study, future research should examine whether pressure pain sensitivity predicts the onset of self-harm and suicide attempts.
This was an exceptionally interesting project to work on, and my deepest thanks go to Mac, Professor Dennis Ougrin, Mr Oliver English, and Professor Helen Minnis for making this study possible.
Rangitoto Island, Auckland, New Zealand. Photo taken by a family member