Do depressed people experience more physical pain – or less?

Recent global burden of disease surveys tell us that pain and depression are two of the most common and pervasive issues in modern society. The fact that these two are also highly comorbid hardly generates surprise. Living with chronic pain often means restricted mobility, reduced capacity to work and general impairment of quality of life, in addition to the general unpleasantness of the pain, so mood will inevitably suffer.

Less intuitive, perhaps, is the suggestion that depression might cause a change in pain, rather than result from it. One theory is that a neurochemical imbalance of monoamines (such as serotonin), which are involved in both mood regulation and the processing of pain processing, could cause both mood disturbance and sensory hypersensitivity, and increase the number and intensity of painful complaints. Patients with depression often report more somatic complaints, such as abdominal pain, back pain and headache (amongst others) compared to those without depression. The usual problems of ascribing causality from clinical data have led researchers to use experimental pain paradigms to compare depressed and non-depressed individuals in their response to noxious stimuli (ice cold water, heat, lasers and similarly fun things). Results from these studies, however, have been startling in their inconsistency. While some have found increased pain in those with depression consistent with clinical data, even more studies have found decreased pain. So which is it – does depression putatively exacerbate or diminish pain?

We conducted a meta-analysis of these studies to try to better understand reasons for the variation in findings. Our search identified 32 relevant experimental studies consisting of a total of 1,317 participants (depressed=641, healthy controls=676). The average age of the aggregated depressed sample was 39 years (74% female), and was 38 years (71% female) for the control sample. Patients were mostly diagnosed with Major Depressive Disorder and pain was assessed using several outcome measures during both anti-depressant medicated and unmedicated states. Pain stimuli included heat, cold, electrical and ischemic (e.g. blood flow restriction via tourniquet followed by handgrip exercises to produce deep muscle pain).

What did we discover? As expected, findings were remarkably varied and much of this variation remains hard to explain. However, one key finding was that the link between depression and pain may be influenced by the type of pain stimulus used. For ischemic inductions, depressed people reported significantly more pain compared to controls (reduced pain threshold and tolerance). For exteroceptive skin stimulation (e.g. heat, cold, electrical), depressed people tended to demonstrate less pain (or no difference). We also found a moderately analgesic effect of anti-depressant medication. Full results are published in the Journal of Pain and the clinical implications of the findings will be considered in the JoP’s December edition of Journal Club.

Explaining this apparent stimulus effect is difficult given that the available data does not allow direct insights into underlying mechanisms. One speculative interpretation that seems to fit neatly is provided by Lautenbacher and Krieg’s global theory of pain processing in psychiatric disorders. In a nutshell, this theory suggests that neurotransmitter dysfunction in depression: (1) globally diminishes processing of all sensory input, and (2) disrupts pain pathways that produce ‘natural’ analgesia that occur as a defence against pain that is sustained or interoceptive in origin (e.g. muscle or joint pain). This could explain why pain might be generally diminished in depression – except when pain is evoked through nociceptors innervating deep structures (e.g. muscle or joint pain, including that activated by ischemic pain inductions) which might fail to benefit from this natural analgesia. The theory also offers a nice explanatory framework that might contribute to our understanding of not only why findings seem to differ within the experimental literature, but also across clinical (involving interoceptive pain) and experimental (usually involving exteroceptive pain) studies.

It is worth restating that this interpretation of the results is speculative.  There may be several alternative influences – ischemic pain inductions may have been longer, more painful, or different in some other fundamentally important unidentified way. Furthermore, although evidence for ischemic pain differences in particular seems convincing, it is impossible to be absolutely certain of a stimulus effect. While meta-analysis is an extremely powerful technique, chance results or unreliable findings from individual studies are still propagated into the wider aggregated data (albeit with reduced influence). Nevertheless, it is interesting to note that the explanatory theory predates (therefore predicted?) the vast majority of the included empirical studies and a broadly similar pattern of results is suggested by close inspection of a subsequent independent study whose publication date prohibited its inclusion in the review.

Overall, these findings do support a relationship between depression and pain. But they also indicate that this relationship is complex and requires further research. The fact that pain and depression are leading causes of years lived with disability and are commonly comorbid in clinics across the world suggests this research is warranted.

About Trevor Thompson

Trevor Thompson University of GreenwichTrevor Thompson is a senior lecturer in the Psychology department at the University of Greenwich, UK. He has previously worked as a consultant statistician in the area of patient-reported outcomes in the US. He enjoys research examining the neurophysiological foundations of pain and exploring the potential for technology in pain management. But hates mime artists.

Reference

Trevor Thompson, Christoph U. Correll, Katy Gallop, Davy Vancampfort, Brendon Stubbs (2016) Is Pain Perception Altered in People With Depression? A Systematic Review and Meta-Analysis of Experimental Pain Research. J Pain Volume 17 (12); 1257–1272.

Comments

  1. Lesley Singer says

    I was wondering of people do different things when they are depressed and handle it differently causing more changes in the neurochemistry which may affect the way they feel pain it is for sure we need more information and studies done to see what the effects of depression are and maybe have subtypes of depression
    I am sort of glad that is the bottom line as the more we say negative things such as depression increases pin or vice versa it seems to affect the way people will see it regardless.

    trevor thompson Reply:

    Totally agree, Lesley, and it’s a little surprising in many ways that with so much research that our understanding is still so incomplete.

  2. Graham Yates says

    I thought the skin is interoceptive. As Bud Craig tells us it is an organ and therefore interoceptive.
    I feel Richie Davidson’s work would better describe it. Depressives have the same ability to feel joy at looking at pictures of say a mother hugging a child but it diminishes quickly compared to non depressives.The same may go for pain. They may not feel things for good or bad for the same time as non depressives.However ischaemia is a much greater homeostatic threat and therefore will have a far stronger sustained reaction.

    trevor thompson Reply:

    I probably should been a little more precise with the distinction between exteroceptive and interoceptive – and thanks for pointing this out Graham – which I meant in terms of the source of the noxious stimulus, e.g. external (e.g. contact heat pad) or internal (e.g. muscle pain). I agree that ischemia is more threatening and is also likely to differ in several other potentially important ways, and application of the Lautenbacher et al theory is nothing more than speculative. We really need more research to identify precisely what the causal components are that seem to produce different pain responding in depressed individuals for this type of pain.

    graham yates Reply:

    I would still disagree. The pain from a heat pad is not extroceptive, because it is our interoceptive network that creates the messaging of threat. The pain from a kick is not the shoe but the changes in information transmitted via lamina 1 from the alterations in dermal layers from the kick

  3. John Barbis says

    Could it be that the inconsistent pain response is due to our incomplete understanding of what causes depression? Depression may have more causes than just low serotonin levels. Patient responses to NSRI’s and other classic medications are highly variable. Ketamine and some psychedelic compounds have been found to be effective in some patients. Depression may be a description of constellation of symptoms rather than a neuropathology based on a single neurochemical factor.

    EG Reply:

    Microdosing the next big thing, apparently. I can see it gaining traction for difficult cases, but Ketamine appears to have potential side effects. In contrast, LSD and mushrooms are supposed to be very safe, so long as they are pure.

    Microdosing LSD combined with energy psychologies. I can definitely see that being one potential future for chronic pain treatment. The old fashioned approach of ‘start exercising, learn some pain science and stop whingeing’ are numbered, hopefully.

    trevor thompson Reply:

    I think you make an excellent (and very nicely expressed, if I may say) point John. There could be a variety of potentially quite diverse causes of depression which could affect the processing of pain in different ways, even if the end product on mood is the same. It’s nice to think of a simple neurobiological model underlying depression (or any clinical disorder), but things are rarely that simple.