IS THERE A PAIN MODULATION EFFECT WITH BLOOD FLOW RESTRICTION EXERCISE?

Blood flow restriction resistance exercise (BFR-RE) has been shown to reduce pain across a training program in a range of clinical conditions (Ferraz et al., 2017; Giles et al., 2017; Hughes et al., 2019). Interestingly, the reduction in pain with low load BFR-RE appears to be greater than high load exercise (HL-RE). It is logical to assume that this may be primarily caused by the lower loads used during BFR-RE, which places less loading induced strain on a pathological joint or limb. However, recent studies suggest there may be an acute reduction in pain with BFR-RE, or “hypoalgesia effect” (Cook and Koltyn, 2000). 

Exercise is known to decrease sensitivity to pain, an endogenous form of pain modulation termed ‘exercise-induced hypoalgesia’ (EIH) (Koltyn, 2000). Pain desensitisation following exercise is not limited to the exercising limb, and is observed in non-exercising muscles in remote areas of the body (Hughes and Patterson, 2019). This suggests that both local manifestations and spinal / supraspinal nociceptive pathways drive a multi-segmental pain inhibitory effect with exercise. Similarly to other exercise-induced adaptations such as increased muscle strength, the magnitude of EIH appears to be augmented with higher intensity exercise of longer duration (Vaegter, Handberg and Graven-Nielsen, 2014). 

Recent evidence shows EIH occurs when low intensity exercise (e.g. ≤30% 1RM) is performed with BFR (Korakakis, Whiteley and Epameinontidis, 2018; Korakakis, Whiteley and Giakas, 2018). A single bout of low intensity knee extension exercise with BFR was found to reduce anterior knee pain immediately post-exercise in individuals with knee pain, compared to the same exercise protocol without BFR. This effect was sustained for a minimum of 45 minutes, and allowed the individuals to better tolerate exercise with greater loads during this 45 minute period (Korakakis, Whiteley and Epameinontidis, 2018; Korakakis, Whiteley and Giakas, 2018). Although only a subjective measure of pain was used in these studies, it provided the first evidence of a possible hypoalgesia effect with BFR. 

The recent work by Hughes & Patterson (2019 & 2020) investigated hypoalgesia with BFR exercise in greater depth. Initially, the authors published a review paper in Medical Hypothesis, which discussed the literature regarding mechanisms of exercise-induced hypoalgesia with traditional exercise and speculated on possible mechanisms with BFR-RE (Hughes and Patterson, 2019). In this paper, they discussed the possible role of endogenous opioid and non-opioid mechanisms in pain reduction. During intense and painful exercise, opioid and non-opioid substances are released into blood circulation which bind to their target receptors and contribute to pain inhibition. 

To investigate their hypotheses experimentally, 12 subjects, in a randomised crossover design, performed four experimental arms involving dominant limb unilateral leg press exercise (Hughes and Patterson, 2020). Three arms comprised low intensity resistance exercise at 30% of one repetition maximum; one arm was performed with free flow, while the other two were performed with BFR applied continuously at 40% and 80% LOP. The individuals in the low-load arms performed a rep / set scheme of 30 / 15 / 15 / 15 with 30 second interset rest periods. The fourth arm comprised HL-RE at 70% of one repetition maximum, where the individuals performed 4 x 10 repetitions with 53 second interset rest periods. This HL-RE protocol was designed to match the duration of the low-intensity portions of the trial, so that pre- and post-exercise measures of pain were conducted at the same time after completion across all arms. 

The authors measured pain thresholds pre- and post-exercise using mechanical algometry; this was performed in the exercising limb and in remote non-exercising muscles around the body. Blood samples were obtained to examine blood markers of endogenous systems that may contribute to pain inhibition. The authors found that BFR-RE resulted in a greater hypoalgesia effect than free flow low intensity resistance in the exercising limb, as well as remote muscles. The HL-RE group and both BFR-RE groups elicited similar reductions of pain in remote muscles. In the exercising limb, BFR-RE at 40% LOP produced similar pain inhibition as HL-RE, while BFR-RE at 80% LOP produced the greatest hypoalgesia response. Interestingly, pain inhibition was still evident in the exercising limb at 24 hours after exercise in both of the BFR-RE arms. The authors also found increases in circulating plasma beta-endorphin concentration, which is part of the endogenous opioid system and contributed to the hypoalgesia effect. 

Several clinically relevant conclusions can be drawn from the existing literature at present (Hughes and Patterson, 2020).

1. BFR-RE appears to cause acute hypoalgesia that may last for up to 24 hours.
   • This has important implications for patients who may need to tolerate more load during rehab (e.g. painful tendinopathies)
   • Clinicians may be able to have a lasting effect on their patient’s pain in the day after a rehabilitation session.
2. It appears that higher pressure BFR augments the effect on pain. This may partly be driven by endogenous opioid production in response to the muscle discomfort generated during BFR-RE.
3. A systemic effect on pain is observed with BFR-RE, therefore it is possible that an individual can train an unaffected limb with BFR to trigger a reduction in pain in an injured limb, which would be particularly useful in the early stages following injury and surgery (Hughes and Patterson, 2020).

References

1. Cook, D. B. and Koltyn, K. F. (2000) ‘Pain and exercise.’, International Journal of Sport Psychology, 31, pp. 256–277.
2. Ferraz, R. B. et al. (2017) Benefits of Resistance Training with Blood Flow Restriction in Knee Osteoarthritis, Medicine and Science in Sports and Exercise. doi: 10.1249/MSS.0000000000001530.
3. Giles, L. et al. (2017) ‘Quadriceps strengthening with and without blood flow restriction in the treatment of patellofemoral pain: A double-blind randomised trial’, British Journal of Sports Medicine, 51(23), pp. 1688–1694. doi: 10.1136/bjsports-2016-096329.
4. Hughes, L. et al. (2019) ‘Comparing the Effectiveness of Blood Flow Restriction and Traditional Heavy Load Resistance Training in the Post-Surgery Rehabilitation of Anterior Cruciate Ligament Reconstruction Patients: A UK National Health Service Randomised Controlled Trial’, Sports Medicine, 49(11), pp. 1787–1805. doi: 10.1007/s40279-019-01137-2.
5. Hughes, L. and Patterson, S. D. (2019) ‘Low intensity blood flow restriction exercise: Rationale for a hypoalgesia effect’, Medical Hypotheses, 132, p. 109370. doi: 10.1016/j.mehy.2019.109370.
6. Hughes, L. and Patterson, S. D. (2020) ‘The effect of blood flow restriction exercise on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid mechanisms of pain modulation’, Journal of Applied Physiology, 128. doi: 10.1152/japplphysiol.00768.2019.
7. Koltyn, K. F. (2000) ‘Analgesia following exercise: A review’, Sports Medicine, 29(2), pp. 85–98. doi: 10.2165/00007256-200029020-00002.
8. Korakakis, V., Whiteley, R. and Epameinontidis, K. (2018) ‘Blood Flow Restriction induces hypoalgesia in recreationally active adult male anterior knee pain patients allowing therapeutic exercise loading’, Physical Therapy in Sport. Elsevier Ltd, 32, pp. 235–243. doi: 10.1016/j.ptsp.2018.05.021.
9. Korakakis, V., Whiteley, R. and Giakas, G. (2018) ‘Low load resistance training with blood flow restriction decreases anterior knee pain more than resistance training alone. A pilot randomised controlled trial’, Physical Therapy in Sport. Elsevier B.V., 34, pp. 121–128. doi: 10.1016/j.ptsp.2018.09.007.
10. Vaegter, H. B., Handberg, G. and Graven-Nielsen, T. (2014) ‘Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans’, Pain. International Association for the Study of Pain, 155(1), pp. 158–167. doi: 10.1016/j.pain.2013.09.023.