Research Review By Dr. Demetry Assimakopoulos©

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Date Posted:

January 2018

Study Title:

Pain and respiration: a systematic review

Authors:

Jafari H, Courtois I, Van den Bergh O et al.

Author's Affiliations:

Health Psychology Unit, Faculty of Psychology & Educational Science, KU Leuven University, Leuven, Belgium; Department of Clinical Psychological Science, Maastricht University, the Netherlands.

Publication Information:

Pain 2017; 158(6): 995-1006.

Background Information:

Breathing techniques are commonly used to control the symptoms of multiple healthcare issues, such as general distress, anxiety, high blood pressure, and asthma. Specifically, slow, deep breathing (SDB) is routinely used in clinical practice to treat pain. In spite of its ubiquitous use, the efficacy and mechanisms of action of breathing techniques for the treatment of pain remain elusive. The intent of this review was to summarize the literature on the bidirectional association between pain and respiration in both clinical (patients with pain) and experimental (induced pain in healthy individuals) studies. As such, the authors sought to perform a systematic review to summarize and clinically appraise the research on this topic. They also provided direction and ideas for future research.

Pertinent Results:

The Effect of Pain on Respiratory Outcomes:

Four experimental studies examined the effect of a phasic, short-lasting cutaneous pain stimulus on respiration. Sudden cutaneous pain elicited a consistent pattern of decreasing inspiratory time and volume. It is believed that these inspiratory changes in response to pain are centrally driven, as the changes are instantaneous, also occur under general anesthesia and are remarkably similar to the respiratory component of the startle reflex.

Other experimental studies have demonstrated increases in minute ventilation under conditions of experimentally-induced, sustained pain. The increase in minute ventilation is thought to be due to deeper breathing, faster breathing, or a combination of both.

Clinical studies have observed increased respiratory rate (RR) and ventilation asynchrony during a painful procedure, compared to a non-painful procedure. Another clinical study showed hyperventilation in chronic pain patients, which diminished after pain was relieved.

Collectively, the findings of both experimental and clinical studies show that hyperventilation is a response occurring in situations of uncontrollable stress, fear and pain.

It has been proposed that hyperventilation during acute pain reflects the respiratory component of the fight/flight response, which prepares the organism for possible attack or injury (1-3). Acute hyperventilation can also activate endogenous adrenergic and opioid systems. It is uncertain how hyperventilation serves a purpose in chronic pain, as chronic hyperventilation can dysregulate basic physiological processes. (NOTE: Previous reports have proposed that a component of chronic pain may involve a secondary reaction to multi-system dysregulation, including neurological, endocrine and immune components. Purportedly, these systems are interconnected, meaning dysregulation in one system has an effect on the others).

Past works from this group indicated that the mechanism of hyperventilation in the context of chronic pain, or sustained acute pain, may be less specific. The authors suggest that hyperventilation, in this context, does not depend on stimulation of nociceptive receptors, but may reflect the influence of affective, cognitive and evaluative components of the pain experience (i.e. feelings of fear, panic and uncontrollability [4]), in response to an actual or potential aversive event such as pain. While this is an attractive theory, the precise mechanisms underlying respiratory responses to acute, sustained and chronic pains are unfortunately not well understood, and require further study.

The Effect of Respiration on Pain:

The Baroreceptor Reflex: The baroreflex functions to rapidly adjust heart rate (HR) and blood pressure (BP), through receptors within the lung’s blood vessels, aortic arch, carotid sinus and heart chambers. These baroreceptors detect changes in BP, and relay the information to neurons within the nucleus tractus solitarius (NTS) in the medulla, through the vagal and glossopharyngeal nerves. The NTS then projects to vagal/parasympathetic and sympathetic brain stem nuclei, which send an efferent signal to either increase (sympathetic) or decrease (vagal) BP as needed. When BP increases and arterial walls expand, stimulated baroreceptors trigger a decrease in HR and vascular tone. Conversely, a decrease in BP inhibits baroreceptors, causing an increase in HR and vascular tone. Interestingly, this system has a central nervous system branch, which connects the NTS to other regulatory centres in the brain stem and higher cerebral regions related to pain and autonomic control. These connections enable cardiovascular activity to impact higher cerebral regions involved in emotion and cognition, which may provide reciprocal modulation of autonomic outflow and characteristics of baroreceptor function.

Pain and Blood Pressure:

Evidence suggests an inverse association between BP levels and pain sensitivity. This may be a functional association to reduce the impact of pain in stressful and threatening situations. There are several purported mechanisms, including stimulation of baroreceptors to lower cerebral arousal, activation of endogenous opioids, and activation of noradrenergic pathways. The analgesic effect of SDB (slow, deep breathing) on baroceptor reflexes likely depends on several individual and experimental factors, such as mode of baroreceptor stimulation, participant emotional state, intensity of stimulation, age, comorbid pathology, mental stress, and cognitive ability.

Respiratory Sinus Arrythmia (RSA):

HR is known to transiently increase during inspiration, and decrease during expiration. This oscillation within a breathing cycle is referred to as RSA, and is a major source of heart rate variability (HRV). Increasing HR during inspiration occurs because during inspiration, systolic BP naturally drops due to decreased stroke volume. This transient decrease in BP is picked-up via baroreceptors, which leads to an increase in HR. The reverse occurs during expiration, via the vagus nerve. Stronger fluctuations in HR across the respiratory cycle have been observed with slower, deeper breathing. These central and baroreceptor systems play an essential role in the relationship between cardiovascular, respiratory activity and pain dampening through the cardiovascular or central branch of the system. However, the EXACT mechanism remains unclear.

Experimental Studies Evaluating the Effect of Respiration on Pain

Experimental studies have shown variable effects of respiratory phase (inspiration vs. expiration) on pain. There is also great variability on SDB’s exact effect on pain levels in clinical vs. healthy populations. Four of the six included studies found SDB to significantly reduce pain. Two of these studies found that SDB reduced the nociceptive reflex. Interestingly, one study found simple instructions to relax to be effective in diminishing pain, while another showed that breath-holding reduces pain. Overall, the findings are not very consistent; there is no obvious difference between studies that observed a change in pain and those that failed to observe respiratory hypoalgesia. The purported mechanisms of analgesia are also quite variable, as relaxation, distraction and expectation may all contribute to respiratory hypoalgesia through modulation of vagal tone, respiratory sinus arrythmia and baroreflex activity. Changes in these physiological processes are theorized to indirectly affect cardiovascular and autonomic systems; however, this relationship requires further study. The conditions under which SDB may and may not produce hypoalgesic effects is also an important area of future study.

Clinical Studies Evaluating the Effect of Respiration on Pain

Only a limited number of clinical studies have been performed to assess the effect of breathing on pain. Six of the eight studies reported a beneficial effect. Unfortunately, these studies embody a number of methodological biases towards positive findings. Also, three of the studies did not apply their breathing techniques independently from other potentially active therapeutic treatments, such as relaxation, massage, relaxing sounds, and meditation. The variability in the clinical study findings is likely due to the heterogeneity of pain quality, type and intensity, and breathing exercise instructions. In such cases, controlled sample inclusion criteria and standardized breathing exercise instructions are required. Similarly, patient expectations and distraction effects caused by a breathing interventions require better controls.

It is conceivable that increased breathing depth, as opposed to breathing frequency, may play a key role in pain reduction. It has been shown that deep breathing and breath-holding after a deep inhalation could activate the anti-nociceptive effects of baroreceptor stimulation (5, 6) and concomitant increases in vagal activation (7, 8). Collectively, several clinical studies suggest a beneficial effect of SDB on pain. However, more well-documented studies on homogeneous patient groups that control for expectations, demand characteristics and distraction effects are required.

Clinical Application & Conclusions:

The authors performed a systematic review to determine the mechanisms and treatment effects of slow, deep breathing (SDB) on pain. While it is understood that acute pain augments respiratory frequency, flow and volume, the clinical impact of chronic pain on respiration remains unclear. Many clinical studies have shown that SDB can alleviate pain, but experimental studies have not consistently demonstrated an analgesic effect. Studies hoping to understand the mechanism of SDB’s action on pain have also been lackluster and largely inconsistent. Unfortunately, the literature has not been able to ascertain a direct causal association between respiration and pain. However, many have proposed a more plausible indirect mechanism via cardiovascular and autonomic pathways.

Still, multiple questions need to be answered, such as:
  1. Do attention, distraction, expectation and self-control impact the therapy’s ability to control pain?
  2. Can SDB produce analgesic effects beyond those produced by attention, distraction and expectations?
  3. Is cardiovascular (baroreceptor) activity the mediating link? If so, which factors in the baroreflex system are important to acknowledge?
  4. Which other central mechanisms may produce respiratory hypoalgesia?
In summary, we understand that breathing techniques can have an analgesic effect. However, the optimal dose, timing and rhythm necessary to produce analgesia have not been clearly ascertained.

REVIEWER’S COMMENT: It is not always clear who will have an analgesic response to breathing interventions. It is also feasible that breathing interventions need to be tailored to the individual patient, by using different breathing cues and instructions. My advice is to have a couple of different breathing techniques/exercises in your back pocket, and try a few of them towards the end of your assessment. If the exercise provides an analgesic effect, try asking the patient to perform the same exercises at home. It has been demonstrated that anxiety and stress have the potential to greatly impact the experience of pain, as elevated levels of each have been positively correlated with pain ratings and disability. With that being said, if you believe that a patient’s psychoemotional status is having a negative effect on pain, SDB exercises may be a good place to start the rehabilitation process, and enable you to cultivate a trusting relationship with your patient.

Study Methods:

This was a systematic review conducted in accordance with the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The authors accessed multiple databases, and included studies published between 1984-2015 dealing with respiration and pain. The initial search resulted in a high number of possible papers (due to the broad nature of the search terms utilized). As such, the authors excluded papers based on the following criteria:
  1. Articles that focused on cardiovascular and BP without addressing respiration as a primary variable;
  2. Studies that mainly focused on the effect of painkillers on respiratory function; and
  3. Letters to the editor, commentaries or abstracts.

Study Strengths / Weaknesses:

Strengths:
  1. The authors conducted an extensive search, accessing multiple databases and the references of each included article.
  2. The authors took their analysis a step further, by discussing the possible mechanisms through which breathing exercises may affect pain.
Weaknesses:
  1. There was a lack of distinct inclusion criteria.
  2. The authors did not offer any evidence-based clinical recommendations for practitioners. How should breathing exercises be used clinically? Or is the evidence too sparse and heterogeneous to provide meaningful recommendations?
  3. The dose and mode of breathing exercise was not consistent in the literature, and did not allow for meta-analysis.

Additional References:

  1. Van Diest I, Proot P, Van De Woestijne KP, et al. Critical conditions for hyperventilation responses. The role of autonomic response propositions during emotional imagery. Behav Modif 2001; 25: 621–39.
  2. Van Diest I, Winters W, Devriese S, Vercamst E, et al. Hyperventilation beyond fight/flight: respiratory responses during emotional imagery. Psychophysiology 2001; 38: 961–8.
  3. Wilhelm FH, Gevirtz R & Roth WT. Respiratory dysregulation in anxiety, functional cardiac, and pain disorders: assessment, phenomenology, and treatment. Behav Modif 2001; 25: 513–45.
  4. Bogaerts K, Hubin M, Van Diest I, et al. Hyperventilation in patients with chronic fatigue syndrome: the role of coping strategies. Behav Res Ther 2007; 45: 2679–90.
  5. Dworkin BR, Elbert T, Rau H, et al. Central effects of baroreceptor activation in humans: attenuation of skeletal reflexes and pain perception. Proc Natl Acad Sci USA 1994; 91: 6329–33.
  6. Dworkin BR, Filewich RJ, Miller NE, et al. Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension. Science 1979; 205: 1299–301.
  7. Bruehl S, Chung OY. Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain. Neurosci Biobehav Rev 2004; 28: 395–414.
  8. Triedman JK, Saul JP. Blood pressure modulation by central venous pressure and respiration. Buffering effects of the heart rate reflexes. Circulation 1994; 89: 169–79.