Control over spinal nociception can be learned   April 5th, 2019

There is growing evidence that a state of heightened sensitivity of central pain processing pathways is present in chronic pain patients. Hyperexcitability at the spinal level can be assessed by experimentally inducing a nociceptive flexion reflex (NFR) of the lower limb. The NFR is a spinal polysynaptic reflex induced by painful stimuli that allows withdrawal from noxious stimuli. The reflex response is typically quantified by the biceps femoris muscle electromyogram following transcutaneous electrical stimulation of the ipsilateral sural nerve. Since the NFR is considered to be a physiological correlate of pain, the NFR has become a widely used tool in pain research to investigate several aspects of pain processing. Previous research has indeed demonstrated that the NFR threshold is often highly correlated with the subjective pain threshold, and that the magnitude of the reflex response is related to the intensity of self-reported perceived pain.

It is well known that the NFR is subject to powerful modulation of several modifiable and non-modifiable factors (e.g. emotional states, cardiac activity, circadian rhythm). In light of the accumulating evidence attesting to the clinical relevance of the NFR as a measure of spinal nociceptive transmission, it is important to gain more insight into factors influencing the NFR. This will allow future studies to identify and account for the influence of these potential confounders. Moreover, in both therapeutic and preventive approaches it might be of great interest for clinicians to address modifiable factors in a positive way in order to reduce spinal hyperexcitability. 

Via the descending pain inhibition mechanism, a system of endogenous pain control, we are able to attenuate nociceptive input at the spinal level. Evidence has demonstrated that descending pain modulation is under control of cognitive and emotional processes [1-3]. The question arises whether it is possible to learn using cognitive strategies to suppress spinal nociception. For example, can simple coping strategies used by pain patients to distract themselves from pain activate descending inhibitory pathways? Indeed, reduced activity of descending pain inhibitory circuits has been demonstrated in chronic pain populations, and it has been suggested that this might underlie the genesis of chronic pain [4]. Hence, learned control over descending pain modulation would be a promising strategy for chronic pain treatment.

Recently, Ruscheweyh et al. investigated whether it is possible to learn using cognitive-emotional strategies to specifically target descending pathways in order to achieve pain reduction [5, 6]. In these studies, the NFR was used as a feedback parameter for training subjects to regulate their descending pain inhibitory pathways, since the NFR is considered a measure of spinal nociceptive transmission [7, 8]. More specific, healthy young adults were taught to supress their spinal nociception (i.e. NFR magnitude) by self-selected cognitive-emotional strategies under visual feedback of the NFR. Two feedback groups (fixed vs. random stimulation intervals) and a control group without feedback were included (15 subjects each). During three feedback training sessions, subjects were given the opportunity to try various cognitive-emotional strategies, and to select the one that worked best for them. The most popular strategies were mental imagery or relaxation. This training induced significant NFR inhibition, with training success increasing over training sessions. In contrast, sham feedback or no feedback resulted in significantly smaller or absent success in NFR inhibition. Importantly, the reduced NFR magnitude obtained during feedback training was significantly correlated with the concomitant reduction in pain intensity ratings. It was speculated that the NFR suppression was achieved by learning to deliberately activate their descending pain inhibition systems. 

This promising finding was further explored by Bäumler et al. [9]. In view of learned control over descending pain modulation as a new approach to chronic pain, persistence of learning success (i.e. after the end of the training) and transferability (i.e. after completion of the training, NFR suppression can also be achieved in the absence of feedback on the NFR magnitude) of NFR feedback training was investigated. More specific, this study invited 18 healthy adults who succeeded to supress the NFR to less than 80% of baseline in the final feedback training session in one of the previous NFR feedback training studies [5, 6] for two follow-up sessions (approximately four and eight months after their final feedback training session). No further NFR feedback training was performed in the interval. Findings point out that NFR feedback training success was fully maintained at four months and partially maintained at eight months after the end of the training. Also, transfer (i.e. use of the previously learned strategies for NFR suppression without presentation of feedback) was successful. 

The results of Ruscheweyh et al. and Bäumler et al. may serve as a starting point for the application of NFR feedback training in the context of chronic pain. Moreover, these studies further support the necessity to implement treatment strategies focusing on emotions, cognitions, and psychological factors to target central sensitization.

Evy Dhondt

2019  Pain in Motion


Which approach of NFR feedback training would you prefer in view of possible application to chronic pain patients?

⦁ delivering a minimum of painful stimuli to achieve a maximum of NFR suppression

⦁ delivering stimuli at fixed interstimulus intervals instead of variable intervals since predictable stimuli are usually perceived as less unpleasant than unpredictable stimuli

⦁ a combination of both approaches

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References and further reading:  

1. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron 2007;55(3):377-391. 

2. Bingel U, Tracey I. Imaging CNS modulation of pain in humans. Physiology (Bethesda) 2008;23:371-380. 

3. Wiech K, Tracey I. The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 2009;47(3):987-994. 

4. Yarnitsky D. Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 2015;156 Suppl 1:S24-31. 

5. Ruscheweyh R, Baumler M, Feller M, et al. Learned control over spinal nociception reduces supraspinal nociception as quantified by late somatosensory evoked potentials. Pain 2015;156(12):2505-2513. 

6. Ruscheweyh R, Weinges F, Schiffer M, et al. Control over spinal nociception as quantified by the nociceptive flexor reflex (RIII reflex) can be achieved under feedback of the RIII reflex. Eur J Pain 2015;19(4):480-489. 

7. Skljarevski V, Ramadan NM. The nociceptive flexion reflex in humans -- review article. Pain 2002;96(1-2):3-8. 

8. Sandrini G, Serrao M, Rossi P, et al. The lower limb flexion reflex in humans. Prog Neurobiol 2005;77(6):353-395. 

9. Baumler M, Feller M, Krafft S, et al. Learned control over spinal nociception: Transfer and stability of training success in a long-term study. Clin Neurophysiol 2017;128(12):2462-2469.