Fibromyalgia is a chronic musculoskeletal pain disorder of unknown etiology. It is characterized by chronic widespread musculoskeletal pain, fatigue, poor sleep, and mood disturbances, as well as a multitude of associated symptoms. Approximately 2-3% of the general population in the United States and Canada suffer from fibromyalgia and it is more common in women (3.4%) than men (0.5%). Although it may occur at any age, fibromyalgia is most common in adults aged 40-75 years. Currently there are no FDA-approved or Canada Health approved treatments for fibromyalgia.
Because of the diverse nature of its presentation as well as the current lack of guidelines for its diagnosis and treatment, there is no consensus among physicians regarding the diagnosis and management of fibromyalgia.
What is Currently Known About Fibromyalgia
Excerpted from Donaldson, Sella, & Mueller
“The Neuroplasticity Model of Fibromyalgia”
The term “fibromyalgia” means pain of the muscle and surrounding fibrous tissues of the body and has now generally displaced the older term “fibrositis” which was suggestive of an inflammatory or degenerative musculoskeletal disorder. Although still medically classified as a soft tissue rheumatic disorder, as the older term “fibrositis” would imply, fibromyalgia (FM) is more correctly denotative of a generalized, persistent, idiopathic, musculoskeletal pain condition that is associated with the presence of numerous tender points that reliably discriminate this condition from other rheumatic conditions.
The American College of Rheumatology (ACR) (1990) criteria for the diagnosis of fibromyalgia for research purposes are: widespread pain in all four quadrants of the body of at least three months duration and decreased pain threshold. Decreased pain threshold (allodynia) is operationalized by pressure dolorimetry at 18 designated tender point locations and the finding of a minimum 11 of these points as positive for pain at less than 4.0 kg/cm2of applied pressure. Fibromyalgia tender points are generally found throughout the body including the neck, shoulders, chest, back, arms, hips and knees, but the 18 locations designated by the ACR are the most common locations across the majority of patients. The use of the ACR 1990 classification criteria for fibromyalgia provides a sensitivity of 88% and a specificity of 81% in distinguishing fibromyalgia from other musculoskeletal pain disorders. However, while tender point examination is a clinically reliable technique, the presence of many tender points is also associated with depression, fatigue, anxiety, and other somatic symptoms as well as with pain.
Although not included as part of the ACR diagnostic criteria, the fibromyalgia symptom complex, also includes a number of other commonly associated symptoms, including sleep disturbances, morning stiffness, fatigue, poor immediate recall, poor concentration and a decreased ability to multi-task. Added to the ACR 1990 diagnostic criteria for fibromyalgia, these additional associated symptoms have come to be designated as “Fibromyalgia Syndrome” (FMS).
NOTE: Except where otherwise specifically indicated, the term “fibromyalgia” (FM) will be used throughout this paper to designate both the more specific condition of fibromyalgia as well as the broader syndrome itself.
The identification of fibromyalgia is further complicated by the fact that it commonly coexists with other conditions and syndromes such as: arthritis, chronic fatigue syndrome (CFS), depression and generalized anxiety, headache syndromes, irritable bowel syndrome (IBS), mitral valve prolapse (MVP), primary dysmenorrhea, restless leg syndrome (RLS), systemic lupus erythematous (SLE), temporomandibular joint dysfunction syndrome (TMJ), and myofascial pain syndromes (MPS). In particular, fibromyalgia syndrome and CFS have a great many symptoms in common and a number of studies have shown that a majority of those diagnosed with CFS also meet the ACR 1990 criteria for a diagnosis of fibromyalgia and, conversely, that over 50% of persons diagnosed with fibromyalgia also have a current or past diagnosis of CFS. Some researchers have pointed out that whether a person is diagnosed with fibromyalgia syndrome or chronic fatigue syndrome is largely dependent on whether they complain more loudly of pain or fatigue.
Epidemiological studies have revealed fibromyalgia to be primarily a female disorder, with over 80% of all cases being diagnosed in females and prevalent in approximately 2.0% to 3.3% of the North American population generally. There is also evidence that males with fibromyalgia experience fewer symptoms and fewer tender points as compared to females with fibromyalgia. Although fibromyalgia is seen in children, it is primarily prevalent between the ages of 40 and 64, with a mean age in the population of approximately 48 years. Wolfe suggests that many of the elderly population who are diagnosed with arthritis, may actually be suffering from fibromyalgia, thus increasing the incidence rate for the 60 to 79 age range. Onset appears to be associated with a number of different factors including trauma to the neck, low back pain, viral infection, stress, or a combination of these factors. The development of fibromyalgia has been noted to begin with localized pain in most cases, with a clearly increasing tendency for patients with regional and chronic multi-focal pain to develop chronic widespread pain and fibromyalgia syndrome. Fibromyalgia appears to be a chronic and relatively unchanging condition, with up to 85% of those diagnosed with the condition continuing to fulfill the diagnostic criteria after four years and an average length of time in pain reported as 78.7 months.
With the passing of more than 15 years of extensive research and investigation since the development of the ACR classification criteria, the etiology and consequently the treatment of fibromyalgia continue to be poorly understood. Moreover, although now a very small minority, there are still some “doubting Thomases” that insist that fibromyalgia is not a real medical condition.
A number of clinical observations strongly support muscle as the primary origin of fibromyalgia. First, most persons with fibromyalgia clearly cite muscle as the source of their pain and, while many also describe joint stiffness in the mornings and a “bone-deep” aching, radioimaging of bone and joints is almost invariably normal or any noted abnormalities are of insufficient magnitude to explain the intensity of pain experienced. Second, most persons with fibromyalgia experience increased pain during repetitive muscular activity which eases on cessation. Third, persons with fibromyalgia are generally tender over focal areas of muscle, usually at musculotendinous junctions and there is an improvement in pain after these focal areas of tenderness are injected with anesthetics. Fourth, in the majority of cases, fibromyalgia syndrome appears to develop from unresolved focal and regional myofascial syndromes.Finally, Bengtsson and his colleagues used sequential epidural installations of saline, fentanyl, naloxone, and lidocaine to convincingly demonstrate that there is a peripheral muscle component of fibromyalgia pain.
However, while there are numerous clinical observations that point to muscles as the primary origin of fibromyalgia, the ultimately widespread nature of fibromyalgic pain and the many neurosomatic symptoms that are a recognized feature of fibromyalgia syndrome strongly argue for some systemic process underlying this condition. Despite clear epidemiological overlap with many rheumatic disorders (e.g., rheumatoid arthritis, lupus) extensive investigation of blood markers for systemic rheumatalogical disorder have remained inconclusive.
Numerous other more or less “systemic” theories as to the etiology and pathophysiology of fibromyalgia abound, including: central neurotransmitter imbalances, neuroendocrine-immune dysfunction, thyroid hormone resistance, stress-related physiological changes, psychopathology,psychosocial factors, and sleep disturbance (alpha intrusion).
There is a growing body of evidence suggesting the presence of biochemical abnormalities in the fibromyalgia etiology. Such suggested imbalances include: a generalized deficiency of serotonin, low levels of serum tryptophan and other essential amino acids, increased levels of substance P, and low serum levels of the insulin-like growth factor IGF-1. As well, there is evidence of an enhanced pituitary release of adrenocorticotrophic hormones (ACTH) and a low response of this hormone to neuroendocrine tests.
Because early or frequent awakening with non-restorative sleep is an almost universal complaint of persons with fibromyalgia and early research demonstrated that sleep deprivation in healthy persons can lead to generalized muscle pain, dysregulation of central sleep-wake mechanisms has been hypothesized by many researchers as a critical factor in the etiology of fibromyalgia. There are at least six lines of evidence to support the primacy of sleep dysregulation in the etiology of fibromyalgia. First, clinical investigations over the years have consistently shown a strong association between increasing pain and fatigue and poor sleep ratings. Second, a number of studies have demonstrated that persons with fibromyalgia frequently show changes in their sleep physiology, including presence of an alpha intrusion (7-12 Hz) intrusion EEG anomaly during sleep, periodic involuntary limb movements, periodic K-alpha EEG, and apnea-hypoapnea occurring during sleep. Third, when the slow wave sleep of healthy persons is disturbed by noise, these people also manifest alpha EEG sleep anomaly, non-restorative sleep, and diffuse myalgia and fatigue. Fourth, persons with fibromyalgia show measurable diminution in cognitive-performance functions that are susceptible to sleep deprivation. Fifth, unlike those with fibromyalgia, persons with chronic somatoform pain disorder do not generally complain of non-restorative sleep and do not show alpha EEG sleep anomaly. Sixth, retrospective studies show that the alpha EEG sleep anomaly and symptoms of non-restorative sleep may follow a febrile episode.
Moldofsky suggests that this disruption may be attributable to a disturbance in serotonin metabolism. In addition, a study by Bennett and colleagues suggests that a lack of slow wave sleep disrupts the release of GH-1. However, both of these findings have been disputed by other studies and thus the delta-alpha sleep dysregulation theory remains debatable.
Autonomic nervous system imbalance has also been implicated in the development of fibromyalgia. Using power spectral analysis of heart rate variability, a few researchers have pointed out that the basal autonomic state of persons with fibromyalgia is characterized by increased sympathetic and decreased parasympathetic (vagal) tone with associated increased resting heart rate, reduced heart rate variability, and deranged response to orthostatic stress. Quality of life, physical function, anxiety, depression, and perceived stress were found to be moderately to highly correlated with degree of imbalance between sympathetic and parasympathetic tone. Moreover, there is a high incidence of Raynaud’s syndrome associated with fibromyalgia.
Fibromyalgia continues to be defined primarily in terms of the complaint of widespread soft tissue or muscular pain, yet fibromyalgia is clearly much more than just muscle pain. Moreover, the pervasive eclectic symptomatology of the typical fibromyalgia sufferer cannot be explained by any one pathophysiological aberration.
Chronic Benign Pain and Fibromyalgia
Although fibromyalgia has been generally viewed as a muscle pain disorder and traditionally classified as a non-articular rheumatic disease, it also clearly falls within the area of chronic benign pain as defined by the International Association for the Study of Pain (IASP). Chronic benign pain is defined as pain of a non-life threatening nature that lasts for more than six months. After more than a century of failing to adequately explain chronic benign pain in terms of peripheral nervous system (PNS) and/or psychological phenomena, pain researchers are increasingly turning to the neurosciences and investigating chronic pain as a central nervous system (CNS) phenomenon. The preliminary results of these works indicate that the central nervous system (CNS) (including the dorsal horn and the cortex) may react to persistent pain by becoming sensitized, and that plastic changes in the CNS then increasingly become involved in the maintenance of chronic pain. Donaldson and Mueller applied this thinking to fibromyalgia, suggesting that fibromyalgia may involve central as well as peripheral neurological dysfunctions.
Wolfe et al. in their article on the prevalence of fibromyalgia in the general population, made the cogent observation that the “association between fibromyalgia and chronic pain, aging and musculoskeletal deterioration or arthritis suggests that one possible causal relationship for fibromyalgia is other musculoskeletal pain.” Supporting this observation, it has been variously noted that for the vast majority of persons with fibromyalgia their end-state condition was preceded by persistent localized or regional pain.
Certainly, with respect to fibromyalgia, there is strong evidence that persons with this particular benign chronic pain disorder demonstrate a generalized hypervigilance to both pain and auditory stimuli as well as qualitatively altered nociception; with a reduction in pain threshold (allodynia), an increased response to painful stimuli (hyperalgesia, and an increase in the duration of pain after nociceptor stimulation (persistent pain)— all findings that support the hypothesis of centralized pain amplification in fibromyalgia.
There is strong evidence that persistent or chronic noxious stimulation can sensitize both the central nervous system (CNS) and peripheral nervous system (PNS) structures involved in pain perception.This process of central and peripheral neurosensitization is called neural plasticity and is likely a very important factor in the pain experience of persons with fibromyalgia as well as in the development of other “traumatic disability syndromes”such as postconcussion syndrome, post traumatic stress disorder, multiple chemical sensitivity, and chronic pain disorder as well as phantom limb sensations and pain. Neurosensitization or neural plasticity (hereafter referred to as plasticity) refers to changes in reactivity of the nervous system and its components as a result of constant successive activations.As a result of repeated exposure to pain stimulation, plasticity may be seen in the process whereby the CNS or the PNS a) grows in size, b) alters the area(s) of innervation, or c) becomes more responsive to the pain signal. Essentially, plasticity refers to a re-wiring of synaptic connections, which can result in amplification of peripheral inputs, or, if prolonged, a pain state in the complete absence of peripheral input.
Repeated stimulation of the neural pathways by the pain signal can lead to changes in functioning which have a direct impact upon the maintenance of chronic pain. This may be seen as changes in: a) the peripheral sensory neural pathways, b) the afferent from a muscle spindle fiber as it impacts upon the motor neuron pool, and c) the brain itself.
Peripheral Sensory Neural Pathways
Repeated stimulation of a nerve causes it to grow in diameter and to invade more receptor sites than before (especially if these areas are not receiving neural stimulation), potentially affecting a wider area.Repeated stimulation of the receptor sites at the dorsal horn leads to changes in receptor sites, including both a reduction in their threshold of activation as well as increases in extraneous background neural activity, which may stimulate the now more sensitive receptors.
Finally, research has shown that sensory input from muscle, as opposed to skin, is a much more potent effector of CNS sensitization. For example, the pain signal from muscle tissue is larger in amplitude and impacts upon the receptor sites at the dorsal horn for a longer period of time (90 msec) than that of a pain signal from a cut on the skin (15 msec). In most traumas (chronic pain situations), when connective tissue is involved, increased pain may be expected.
Muscle Spindle Fiber Afferent
Stretching a muscle upon its length will not only produce tissue damage (tearing of the sarcoma causing leakage of calcium, potassium and other biochemicals into the surrounding tissue), but also alters the afferent generated by the muscle spindle fibers, furthercompounding the problem. The type of contraction that the muscle is undergoing immediately before the stretch determines the manner in which the afferent is altered. If the muscle is in an eccentric (lengthened) position, the afferent generated immediately after will be decreased, whereas if the muscle is in a concentric (shortened) position the subsequent afferent will be increased. This is why knowledge of the positioning of the person at the moment of trauma is so important in understanding the resulting muscle injury and dysfunction. For example, if a person is in a rotated position (i.e., head turned to the left) one muscle out of the homogeneous pair must lengthen while its contralateral partner must shorten for rotation to occur. If the insult is recent (within 6 weeks) the experienced pain most likely involves inflammation. However, if the pain persists beyond six weeks it probably involves taut bands and trigger points which may be located within the injured muscle itself or in other muscles of the same myotatic unit. As the timeline increases, it is reasonable to expect more involvement with trigger points and less from inflammatory processes. Surface electromyography (sEMG) can be used after the swelling has gone down to document the changes in afferent and direct neuromuscular retraining.
As the length of time post injury increases, it can be expected that the number of trigger points will also increase due to the development of secondary or satellite trigger points. Whether this is due to a change in the biomechanical aspects of the muscle activity about the joint (see below) or alterations in the neural pathways (see below) or a combination of these factors is not clear. Also it is not entirely clear why trigger points spread more rapidly in one person versus another, although stress-related physiological differences and genetic factors are suspected.
It is only recently that researchers have started to examine the impact of chronic pain upon the brain. While many health care practitioners regard the brain as a passive recipient of the pain signal, current research suggests that the brain is very much involved in the perception of pain and reacts to constant stimulation by the pain. This reaction is just starting to be understood. In the dorsal horn, repeated stimulation appears to sensitize the CNS, requiring less stimulation for reaction and creating more intensity in that reaction. In addition, the neural plasticity model suggests the brain's reaction may become independent of the peripheral pathology as seen in the development of phantom limb pain. This latter phenomena has been demonstrated and reported by various authors such as Coderre and Birbaumer.
The evidence for changes in brain functioning as a result of repeated noxious stimulation is quite persuasive.With respect to fibromyalgia, a number of researchers have reported findings supporting an association with changes in brain functioning. For example, persons with fibromyalgia have been shown to produce amplified cerebral evoked potentials as compared to normals in response to noxious heat stimulationand fibromyalgia patients characterized by lower pain thresholds show decreased regional blood flow in the thalamus and caudate nucleus compared to normal controls. Flor-Henry has found characteristic EEG abnormalities involving the power distribution of theta (4-7 Hz) and high beta (20-50 Hz) brain waves in persons with fibromyalgia as compared to normals. Similarly, Donaldson and Mueller have reported that the EEG power distribution of the brain, particularly in the frontal cortex changes in fibromyalgia patients, and improvement in symptoms was correlated with changes in this power distribution.
Evidence indicates that the nervous system is dramatically altered by persistent injury and by noxious inputs produced by the injury. Coderre goes on to state “ in some cases peripheral tissue damage or nerve injury leads to a pathological state characterized by one or more of the following: pain in the absence of a noxious stimulus, increased duration of response to brief stimulation, reduced pain threshold, increased responsiveness to suprathreshold stimulation, and spread of pain and hyperalgesia to uninjured tissue” (p. 259).
Thus, it is believed that as with all neural systems, the more the system is stimulated, the more efficient it becomes and the more easily it is stimulated; in the end requiring ever less intense and fewer stimuli to cause more pain.
The Pain from Fibromyalgia Is Real,
Many people with fibromyalgia – a debilitating pain syndrome that affects 2 to 4 percent of the population – have faced the question of whether the condition is real.
Fibromyalgia often has been misdiagnosed as arthritis or even a psychological issue. Increasingly, though, the scientific knowledge about fibromyalgia is growing, and a new paper from the University of Michigan Health System says there are “overwhelming data” that the condition is real, is characterized by a lower pain threshold and is associated with genetic factors that can make some people more likely to develop fibromyalgia.
The review paper, in the December issue of the journal Current Pain and Headache Reports, cites recent studies involving pain, genetics, brain activity and more. The paper's authors hope these findings will lead to a better understanding and acceptance of fibromyalgia and related conditions.
“It is time for us to move past the rhetoric about whether these conditions are real, and take these patients seriously as we endeavor to learn more about the causes and most effective treatments for these disorders,” says Richard E. Harris, Ph.D., research investigator in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the U-M Health System's Chronic Pain and Fatigue Research Center.
A growing amount of research related to the neurobiology of this condition supports the notion that the pain of fibromyalgia is real. Studies at U-M and elsewhere using two neuroimaging techniques – functional magnetic resonance imaging (fMRI) and single photon emission computed tomography (SPECT) – indicate there is a difference between patients with and without fibromyalgia.
“In people without pain, these structures encode pain sensations normally. In people with fibromyalgia, the neural activity increased,” says Daniel J. Clauw, M.D., director of the U-M Chronic Pain and FatigueResearchCenter and professor of rheumatology at the U-MMedicalSchool, and an author of the new paper. “These studies indicate that fibromyalgia patients have abnormalities within their central brain structures.”
In a 2003 paper in the journal Science, a U-M team reported that a small variation in the gene that encodes the enzyme called catechol-O-methyl transferase, or COMT, made a significant difference in the pain tolerance, and pain-related emotions and feelings, of healthy volunteers. Researchers also have found that individual mutations in the COMT gene are related to the future development of temporomandibular joint disorder, also known as TMD or TMJ, a condition related to fibromyalgia.
Together, these studies about COMT and numerous studies with animals suggest that pain sensitivity is determined at least in part by a person’s genetic makeup, Clauw says.
The authors note that there are some legitimate areas of debate regarding fibromyalgia, including disagreements about how precisely it should be defined and whether people with the condition deserve compensation. But none of those disagreements should detract from the acceptance of it as a condition causing real pain, they say.
Reference: Current Pain and Headache Reports, Dec. 2006, pp. 403-407.
Spreading of Pain: Women vs. Men
Posted: August 28, 2008
Fibromyalgia occurs more often in women, although men get this painful condition too. While many reports have documented that healthy women have a lower pain threshold than healthy men, this does not explain why more than twice as many women develop fibromyalgia.
Quite often, fibromyalgia is triggered by muscle pain in one area (due to an injury or fall) that eventually spreads, or refers, to the whole body. In addition, once symptoms of fibromyalgia are present, it is common for the regional pain caused by myofascial trigger points to produce a referral of pain. Myofascial trigger points (MTPs) are regions in a muscle with tense, ropey bands that feel like firm knots. Pressing on an MTP hurts, and it also refers pain to other muscle areas. This spreading pain is a common phenomenon, but it is not known if it varies between men and women.
A research study presented at the 2008 American Pain Society meeting investigated whether local and referred pain is different between women and men* A University of Iowa research team recruited 69 healthy volunteers (35 female, 34 male) and injected a painful acidic solution into the mid-belly of their back calf muscle to determine if the spread or referral of pain was different between the sexes.
The average pain ratings at the site of the acidic injection was the same for the two groups (women and men) ... an important observation because it means that women do not simply complain more about their pain. Of the participants, 62 percent experienced a referral or spreading of pain from the middle of the calf down to the back ankle region. Looking specifically at the group of volunteers who referred pain, women outnumbered the men two to one. Ironically, this is the same distribution ratio of reported widespread pain in the general population.
The study authors state that the referral or spread of pain likely occurs by a central nervous system mechanism when the pain at a regional muscle site exceeds a certain threshold. Given that women do have lower pain thresholds, this could partially explain why women are more likley to experience the spreading of pain and may be why more women develop fibromyalgia. And although a smaller portion of male volunteers in this study developed referred pain, these findings also support the fact that there is a subgroup of men that may be more susceptible to getting fibromyalgia.
Aside from helping to explain the higher prevalence of fibromyalgia in women, this study offers insight on the importance of treating MTPs—for both women and men. Not only do MTPs refer pain to other areas (which provides a strong case to get them treated post haste), they also increase the number of pain signals going to the central nervous system. This, in turn, can cause a magnification of the "whole body" pain of fibromyalgia.
Many treatments may help relieve or reduce the pain of MTPs, such as massage, injecting the MTP with an anesthetic, frequency specific microcurrent, low level laser therapy, application of moist heat or coolant spray and then gently stretching the affected muscles, and various hands-on physical therapy techniques. In addition, factors that may enhance the development of MTPs should be addressed. This may include getting quality sleep, improving the way you use your muscles to avoid straining them, and eating healthy so that your muscles are adequately nourished.
* Frey Law L, et al.J Pain 9(4 suppl 2):P9 Abs #134, 2008
A Pilot Study of the Efficacy of Heart Rate Variability (HRV) Biofeedback in Patients with Fibromyalgia
by AL Hassett, et al
Journal: Applied Psychophysiology and Biofeedback. January 12, 2007.
Authors and affiliation: Hassett AL, Radvanski DC, Vaschillo EG, Vaschillo B, Sigal LH, Karavidas MK, Buyske S, Lehrer PM. Department of Medicine, Division of Rheumatology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. [E-mail: firstname.lastname@example.org ]
Introduction: Fibromyalgia (FM) is a non-inflammatory rheumatologic disorder characterized by musculoskeletal pain, fatigue, depression, cognitive dysfunction, and sleep disturbance. Research suggests that autonomic dysfunction may account for some of the symptomatology of FM. An open label trial of biofeedback training was conducted to manipulate suboptimal heart rate variability (HRV), a key marker of autonomic dysfunction.
[Note: Autonomic dysfunction, or dysfunction of the autonomic nervous system (ANS) is known as dysautonomia. The autonomic nervous system regulates unconscious body functions, including heart rate, blood pressure, temperature regulation, gastrointestinal secretion, and metabolic and endocrine responses to stress such as the "fight or flight" syndrome. As regulating these functions involves various and multiple organ systems, dysfunctions of the autonomic nervous systems encompass various and multiple disorders.]
Methods: Twelve women ages 18-60 with FM completed 10 weekly sessions of heart rate variability biofeedback. They were taught to breathe at their resonant frequency (RF) and asked to practice twice daily. At sessions 1, 10, and 3-month follow-up, physiological and questionnaire data were collected.
[Note: resonant frequency means breathing at a frequency that matches or resonates with the heart rate.]
Results: There were clinically significant decreases in depression and pain and improvement in functioning from Session 1 to a 3-month follow-up.
For depression, the improvement occurred by Session 10.
Heart rate variability and blood pressure variability (BPV) increased during biofeedback tasks.
Heart rate variability increased from Sessions 1-10.
While blood pressure variability decreased from Session 1 to the 3 month follow-up.
Conclusions: These data suggest that heart rate variability biofeedback may be a useful treatment for FM, perhaps mediated by autonomic changes.
While heart rate variability effects were immediate, blood pressure, baroreflex, and therapeutic effects were delayed. This is consistent with data on the relationship among stress, HPA axis activity, and brain function.
[Note: The baroreflex is a bodily mechanism for maintaining blood pressure. Normally, it provides a feedback loop so that an elevated blood pressure “reflexively” causes blood pressure to decrease, and vice-versa.]