noigroup logo

Mirror pains and icebergs – Neuroscience Nugget No. 7

By Timothy Cocks Neuroscience Nuggets 12 Jun 2014

For people who realise the value of therapeutic story telling, there should be a new joy in reading neuroscience literature with so much of the science forming the basis of analgesic narrative. Mirror pains, once a perplexing and worrying symptom now have an analgesic narrative involving the spinal cord and immune system and a recent paper in Pain by Cheng et al (2014) has provided greater depth to the story.

Mirror-image pain, or simply mirror pain, is the same pain (area and nature) experienced on both sides of the body, usually after trauma or inflammation in one limb. The pain on the side contralateral to the problem is usually not as severe as that on the side of injury. Mirror pains have been documented after injury to, or inflammation of, peripheral nerves and are also experienced in chronic pain states such as CRPS (Milligan et al 2003).

Explaining mirror pains in the past was a real challenge – I tried to make up explanations for patients, such as that it was new or different use of the limb, but for me (and surely the patient) it was always unconvincing. And imagine the patient’s distress and fear if they thought their problem/injury was now spreading to the other side and seemingly out of control.

In 2003 a paper by Milligan et al demonstrated that mirror pains have an immune system basis. By injecting an immune activating compound around the sciatic nerve of rats at the mid thigh level, they created a sciatic inflammatory neuropathy and noted a mechanical allodynia on the same side. When more compound was injected (still into just the one leg) producing a more intense immune response, bilateral allodynia was noted. Both ipsi- and contralateral allodynia were rapidly reversed when substances that inhibit the activity of glial cells or reduced pro-inflammatory cytokines were injected near the spinal cord.

Since Milligan et al’s (2003) seminal paper on mirror pains there has also been some interesting findings related to changes in sensation in mirror regions -bilateral abnormal sensory function has been noted in patients with unilateral neuropathic pain (Konokka et al 2012) and researchers testing out a new dental digital force transducer noted coincidentally that normal teeth on the opposite side to diseased teeth demonstrated lower mechanical thresholds compared to healthy volunteers (Khan et al 2007).

The recent paper by Cheng et al (2014) in Pain has taken the understanding of the mechanism of mirror pains further. The authors propose a complex chain of events as follows:

Following spinal nerve ligation (peripheral nerve injury) on the right side, tumor necrosis factor alpha (TNF-a) is increased greatly in the ipsilateral dorsal root ganglion (DRG), diffuses to the contralateral DRG via cerebrospinal fluid, and then activates satellite glia on the left side. Activated satellite glia in the contralateral DRG produce excess nerve growth factor which, in turn, enhances nociceptive excitability. Hyperexcitable nociceptors on the contralateral side evoke mirror pain in response to non-noxious mechanical stimuli. pp 918


Now the bit about icebergs. In order to be able to interact with people in pain and help them effectively with some neuroscience knowledge and nuggets – that bit of the iceberg that you can see above the water, you really need to know a whole lot about pain science – the much bigger bit of the iceberg below the water. Having the depth of knowledge provide credibility, confidence and the ability to answer tricky questions from patients accurately. The preceding discussion regarding dorsal root ganglia, TNF-alpha, nerve growth factor and activated satellite glial cells forms the bit of the iceberg below the water for mirror pains, the bit above the water, the narrative you deliver; the neuroscience nugget, might be quite simple:

“Mirror pains are reasonably common and we now know quite a bit about them. In response to your injury and all the circumstances surrounding it (e.g no explanations, failed treatment to date, work pressure etc etc) your nervous and immune systems; systems that know who you are and how to look after you, have determined that you could do with a bit more sensitivity, a bit more protection, so they have made some chemicals to do just this.

There are no fences in the nervous system, and we now understand that these chemicals can leak and spread around a bit and as a result activate and sensitise nerves on the other side of your spinal cord. When this happens, these nerves associated with the opposite side of your body, can start firing off powerful danger signals that your brain can use to construct a pain experience. It’s almost as if your brain wants to keep you doubly safe and has made twice as much of you hurt in order to really protect you! But don’t worry, we also know that this sensitivity will settle down – a good explanation, time and some healthy movement will all help……….”


David Butler and Tim Cocks


Cheng CF, Cheng JK, Chen CY, Lien CC, Chu D, Wang SY and Tsaur ML (2014) Mirror-image pain is mediated by nerve growth factor produced from tumor necrosis factor alpha-activated satellite glia after peripheral nerve injury. Pain 155 906-920

Khan AA, Owatz CB, Schindler WG, Schwartz SA, Keiser K and Hargreaves KM (2007). Measurement of mechanical allodynia and local anesthetic efficacy in patients with irreversible pulpitis and acute periradicular periodontitis. J. Endod. 33, 796–799

Konopka KH, Harbers M, Houghton A, Kortekaas R, van Vliet A, Timmerman W, den Boer JA, Struys MMRF, van Wijhe M (2012). Bilateral Sensory Abnormalities in Patients with Unilateral Neuropathic Pain; A Quantitative Sensory Testing (QST) Study. PLoS ONE 7(5): e37524. doi: 10.1371/journal.pone.0037524

Milligan ED, Twining C, Chacur M, Biedenkapp J, O’Connor K, Poole S, Tracey K, Martin D, Maier SF and Watkins LR (2003). Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. The Journal of Neuroscience 23: 1036-1040.


“Neuroscience nuggets”

Neuroscience nuggets are information nuggets – pieces of biological information based on statement or metaphor that can be used as educational analgesia, explicit education or part of overall story telling. We have collected over 100 of these for a book and will release one or two a week with a short description and references if appropriate.


Explain Pain 2nd Ed, the Graded Motor Imagery Handbook and all noigroup courses are all bursting at the seams with the latest and greatest neuroscience nuggets; click on the links to get your hands on a copy or to find a course near you.


  1. Another great blog guys..! I like to use this little saying….’Keep it simple, explain the science, empower movement, engage the mind and the rest should come..’

    Keep up the good work and spreading the Nuggets 🙂

  2. Thank you boys, this is beautiful and, I think for the first time makes sense to me………. I know I keep referring back to Geoff Maitland but back then Geoff had observed that when a patient presented with bilateral signs and symptoms he alway said “Treat the primary side first and you’ll probably find the other side clears of it’s self, but don’t ask me why”.
    It’s just an example that, even without knowing why patients can also profit from experiential knowledge. Let’s not forget that……..That is the true “art” of practicing medicine without which no amount of knowledge will help…….
    DB London

  3. Hi, thanks again for another nugget. It got me to thinking as to why some people with a chronic one sided problem, don’t get any mirror pain. Patients love to second guess practitioners, so in the interests of adding to the iceberg below the water I’m wondering if anyone has any theories as to why some patients don’t get mirror pain?

    1. timcocks0noi

      Great question Nigel. I’d respond with the following:

      1. We don’t know!

      2. Looking at the research closely, it seems that the kind of mirror pains produced in rat models occur when there is a peripheral nerve injury and there is a significant amount of TNF alpha and other cytokines produced at the spinal cord – if these conditions are not met, then perhaps not every chronic pain state will have mirror pains.

      3. Extrapolating and speculating – humans ARE fearfully and wonderfully complex, and neuroimmune responses to injury and the construction of a pain experience are especially so, but this might be a clue. IL-6, a proinflammatory cytokine that has been linked to mirror pain (Milligan et al 2003), was shown to be increased in experimental subjects who demonstrated pain catastrophising cognitions (Edwards, Kronfli et al 2008). Edwards et al suggested that “Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro-inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.” This might lead one to speculate that there could be a link between pain related cognitions and the development of mirror pains – more simply, if you think you’re in a lot of trouble after an injury, your neuroimmune system might make more pro-inflammatory cytokines as part of a protective response that could set this whole process off.

      Thanks again for the great question Nigel,

      Edwards RR, Kronfli T, Haythornthwaite JA, Smith MT, McGuire L and Page GG (2008). Association of catastrophizing with interleukin-6 responses to acute pain. Pain 2008 Nov 15:140 pp135-44.

  4. Thanks for the post. Continuing to confirm what is sugggested. A recent article published this month on tendinopathies further showing bilateral structural changes in achilies tendon when patient had unilateral chronic achillies pain. Suggesting the central nervous impact on this. Always good reads.

  5. Tanja

    What do you think about sudden pain in both feet at the same location. No injury, but lots of work and life related stress and lots of walking and exercise. Same with sudden pain in both wrists, without injury and additional sudden pain in both hamstrings, without injury. Developed over the course of 9 months. No MRI or Blood findings. Do you think that there’s also a peripheral nerve problem? Nerve conducting speed in the legs is normal.

    I’m interested in your thoughts. Thank’s a lot for your great work.

Your email address will not be published. Required fields are marked *


Product was added to cart.