|
|
Why You Hurt
by Robert M. Bennett MD, FRCP
ImmuneSupport.com
05-20-2000
Those of you who are reading this probably or probably know someone who has fibromyalgia or even suffer from it yourself. Fibromyalgia tends to be treated rather dismissively, sometimes with cynical overtones.
When I trained in London some 30 years ago this diagnosis was never mentioned; even though I trained with one of the foremost rheumatologists in the world at that time. In the United States fibromyalgia has become a semi-respectable diagnosis within the last 10 years, but even so it has some critics. The problem for doctors is that fibromyalgia is not a problem that can be understood in terms of the classical medical model.
This is the model that is used in all medical training. It is based on the correlation of specific tissue pathology with distinctive symptoms (e.g. tuberculosis of the lung causing a chronic cough). Elimination of the causative agent (e.g. the tubercle bacillus) cures the disease.
This model has led to most of the major advances in medicine that we benefit from today. I have seen over 5000 fibromyalgia patients over the past 20 years; most want to be reassured that their symptoms are the product of a "real disease" rather than figments of a fertile imagination - commonly ascribed to psychological diagnoses such as somatization, hypochondriasis or depression.
The good news is that contemporary research is hot on the track of unraveling the changes that occur within the nervous system of fibromyalgia patients. The basic message is that fibromyalgia cannot be considered a primarily psychological disorder; but as in many chronic conditions psychological factors may play a role in who becomes disabled and may even up-regulate the central nervous system changes that are the root cause of the problem.
The Problem: Disordered sensory processing
In this lecture I will try to convey to you what we mean by "disordered sensory processing". It is not easy to understand, unless you have some medical training. However, even a superficial understanding of this topic will change the way you think about the fibromyalgia problem.
Furthermore recent advances, that have been made at the molecular level, hold out the promise of more effective treatment for fibromyalgia pain. The rest of this handout is rather technical and is meant more as a reference that you can refer to after the lecture and in the weeks and months ahead, as you try to understand the exciting progress that is being made.
What is Fibromyalgia?
Fibromyalgia is a chronic pain state in which the nerve stimuli causing pain originate mainly in the muscles. Hence the increased pain on movement and the aggravation of fibromyalgia by strenuous exertion.
Pain is a universal experience that serves the vital function of triggering avoidance. A few unfortunate individuals have a congenital absence of pain sensation; they do not fare well due to repeated bodily insults that go unnoticed. As a physician I see patients with an acquired deficiency in pain sensation (e.g. diabetic neuropathy or neuro-syphilis) who develop a severe destructive arthritis -a result of repeated minor joint injuries that are overlooked.
Thus pain sensation is a necessary part of being human. Pain sensation is a fact of all life. Even the primitive ameba takes avoiding action in the face of adverse events. In such primitive life forms pain avoidance is a purely reflex action, as they do not have the complexity of a highly developed brain to feel pain in the sense that humans do.
Thus every day experience teaches us that there are at least two components to pain in humans: 1. The unconscious reflex avoidance reaction that is so rapid that it-occurs before the actual awareness of the pain sensation (as in all life forms), 2. the actual experience of the pain sensation (that can only occur in highly complex organisms). This is an important point, as it implies that different parts of the brain are involved in these two consequences of a pain reaction.
Over the last few years a number of important research discoveries have started to clarify the enigma of chronic pain. Many of these have a special relevance to the chronic pain of fibromyalgia. The cardinal symptom of FM is widespread body pain {Wolfe, Smythe, et al. 1990 ID: 210}.
The cardinal finding is the presence of focal areas of hyperalgesia, the tender points {Wolfe, Smythe, et al. 1990 ID: 210}. Tender points imply that the patient has a local area of reduced pain threshold -suggesting a peripheral pathology {Bennett 1993 ID: 1149}.
In general tender points occur at muscle tendon junctions, a site where mechanical forces are most likely to cause micro-injuries {Armstrong, Warren, et al. 1991 ID: 1501}. Many, but not all FM patients, have tender skin and an overall reduction in pain threshold {Cohen & Quintner 1993 ID: 1442}. These latter observations suggest that some FM patients have a generalized pain amplification state. There has been a recent plethora of experimental studies apposite to the pathophysiological basis of both the peripheral and central aspects of pain.
The Pathophysiological Basis for Chronic Pain
The International Association for the Study of Pain (IASP) defines pain as follows {Merskey & et al 1994 ID: 2874}:
"Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in tenns of such damage". This definition explicitly affirms that pain has both a sensory and an affective/evaluative component and furthermore acknowledges that it may occur in the absence of obvious peripheral or visceral pathology.
To fully understand chronic pain one must integrate the sensory and affective/evaluative elements of the pain experience. It is equally misguided to focus exclusively on the psychological aspects of pain, as it is to address only the sensory component and ignore the affective dimensions. However for the sake of clarity each of these two constitutive elements will be considered separately.
1. The Sensory Component
Pain is generally envisaged as a cascade of impulses that originate from nociceptors in somatic or visceral tissues. The impulses travel in peripheral nerves with a first synapse in the dorsal horn, a second synapse in the thalamus and end up in the cerebral cortex and other supraspinal structures.
This results in an experience of pain and the activation of reflex and later reflective behaviors. These reflex and reflective behaviors are aimed at eliminating further pain. The expectation is that this nociceptor driven pain will be successfully abolished, allowing healing and a return to a pain free state. The problem with chronic pain is that the linear relationship between nociception and pain experience is inappropriate or even absent, and the expected recovery does not occur.
It is a common misconception to view the nervous system as being "hard wired" -that is stimulation of a nerve ending (say a needle prick) always produces the same behavioral and affective response. This concept implies that the same intensity of pain stimulus will always elicit the same degree of nerve stimulation and hence the same subjective experience of pain.
It is now understood that this concept is wrong. Some 30 years ago Melzack and Wall proposed that pain is a complex integration of noxious stimuli, affective traits and cognitive factors {Melzack & Wal11965 ID: 1227}. In other words the emotional aspects of having a chronic pain state and one's rationalization of the problem may both influence the final experience of pain.
Mendell and- Wall provided the first experimental evidence that the nervous system was not hard wired in 1965 {Mendell & Wall 1965 ID: 2886}. They noted that repetitious stimulation of a peripheral nerve, at sufficient intensity to activate C-fibers, resulted a progressive build up of the amplitude of the electrical response recorded in the second order dorsal horn neurons {Mendell & Wal11965 ID: 2886}. If the system had been hard wired each stimulus should have elicited the ~ response in the second order neuron. They termed this phenomenon "wind-up. It is now appreciated that the phenomenon of wind-up is crucial to understanding the problem of chronic pain via the mechanism of "central sensitization".
Central sensitization refers to an increased activation of second order neurons in the spinal cord; resulting form injury or inflammation induced activation of peripheral nociceptors. Sensory input from muscle, as opposed to skin, is a much more potent effector of central sensitization. This may be the clue to the role of muscle pain in the total spectrum of the fibromyalgia syndrome. A common example central sensitization is post-herpetic neuralgia. Previous injury to a peripheral nerve leads to an amplification of both nociceptive and non-nociceptive impulses.
The mechanism responsible for the abnormal perception of non-nociceptive impulses in post-herpetic neuralgia is an increased excitation of second order nociceptive neurons in the dorsal horn of the spinal cord {Gracely RH 1997 ID: 3056}. A special example of central pain occurs when there is pathology within the central nervous system. This occurs in a thalamic stroke -severe unilateral pain, often accompanied by strong emotions that occurs in the absence of any peripheral nociceptive input.
There are 2 forms of second order spinal neurons involved in central sensitization: 1. Nociceptive - specific neurons -respond only to nociceptive stimuli, and 2. Wide dynamic range neurons -respond to nociceptive and non-nociceptive afferent stimuli. Both may be sensitized by nociceptive stimuli leading to central sensitization, but wide-dynamic range neurons are generally more intensely sensitized than nociceptive-specific neurons.
Nociceptive and non-nociceptive peripheral nerves often converge onto the same wide dynamic range neuron (see figure ). Once sensitized by ongoing nociceptive impulses from peripheral nerves, wide-dynamic range neurons will respond to non- nociceptive stimuli just as intensely as they did prior to sensitization. This results in sensations such as light touch to be experienced as pain (i.e. allodynia).
Sensitization of wide-dynamic-range neurons by prior pain stimuli provides the pathophysiological foundation for non- nociceptive pain. There is emerging evidence that afferent activity , from Golgi tendon organs and muscle spindles, can be converted into pain signals under the influence of central sensitization. For instance some patients with strokes and spinal cord injuries develop severe pain on movement.
Beric has proposed the term "proprioceptive allodynia” to describe this phenomenon 12. He describes such individuals as: "while not experiencing pain at rest, they develop excruciating burning and tingling, often difficult to describe, that appear only when trying to hold an object, move a limb, stand or walk". Thus everyday muscle activity may cause pain and impair function in some individuals with central sensitization. At a physiological level, pain on movement implies that proprioceptive afferents are projecting onto second order wide-dynamic-range spinal neurons, that have been sensitized by previous nociceptive activity.
Thus the central nervous system of subjects who have ongoing pain (e.g. arthritis) or have had previous pain experiences (e.g. post injury pain) may be permanently altered due to changes that can now be understood at the physiological, molecular and structural levels13. At a clinical level this is seen as persistent pain in survivors of serious illnesses who experienced high levels of pain during hospitalization 14, persistent pain after breast surgery 15 or the occurrence of fibromyalgia after automobile accidents 16.
The reason why the phenomenon of central sensitization only occurs in a minority of individuals is not currently known. At a molecular level there are many studies demonstrating the important role of excitatory amino acids such as glutamate, neuropeptides such as substance P, in the generation of central sensitization 17-20. Substance P and CRGP are
important neurotransmitters in lowering the threshold of synaptic excitability, whichpermits the unmasking of normally silent interspinal synapses and the sensitization of second order spinal neurons21-23. Substance P, unlike the excitatory amino-acids, can diffuse long distances in the spinal cord and sensitize dorsal horn neurons in spinal segments both above and below the input segment --with resulting pain signal generation
from non-nociceptive afferent activity. Clinically this will lead to an expansion of receptive fields; e.g. the spread of pain from to uninjured areas after an automobile accident.
2. The psychological component
It was seen in the preceding section that chronic pain could occur in the absence of on going tissue damage -this is an example of the sensory component of pain. It was also noted that one component of pain is a reflex avoidance behavior that can occur before the conscious appreciation of pain. In terms of brain physiology this implies that more primitive parts of the brain are being activated (i.e. the areas below the cerebral cortex).
These sub-cortical areas of the brain contain several discrete nuclei (e.g. the thalamus, cingulate gyrus, hippocampus, amygdyala, and locus ceruleus) which interact to form a functional unit called the limbic system. This is the part of the brain that subserves many reflex phenomena, including the association of sensory input with specific mood states ( e.g. pleasure, fear, aversion ,etc). These facts form the physiological basis for
considering the emotional aspect of pain.
Interestingly electrical stimulation of the brain, during neurosurgical procedures, does not induce pain sensations in pain free subjects. However in past-pain patients it often re-awakens previous pain experiences 24. It is surmised that such stimulation re-activates cortical and subcortical pain circuits that were previously dormant.
It is not known whether there is a single cortical structure that subserves pain memory .Currently, it appears that different cortical and sub-cortical structures are involved in different aspects of the pain experience. For instance removal of the somatosensory cortex does not abolish chronic pain, but excision or lesions of the anterior cingulate cortex reduces the unpleasantness of pain 25.
The anterior cingulate cortex is involved in the integration of affect, cognition and motor response aspects of pain 26 and exhibits increased activity on PET studies of pain patients 27. Other structures involved in cortical pain processing include the prefrontal coortex (activation of avoidance strategies, diversion of attention and motor inhibition), the amygdala (emotional significance and activation of hypervigilance), the locus ceruleus (activation of the "fight or flight" response) 28.
All these structures are linked to the medial thalamus, whereas the lateral thalamus is linked to the somatosensory cortex (pain localization), One example of limbic system activation is the hypervigilance that accompanies many chronic pain states, including fibromyalgia 29.
The emotional component of pain is multifactorial and includes past experiences, genetic factors, general state of health, the presence of depression and other psychological diagnoses, coping mechanisms, and beliefs and fears surrounding the pain diagnosis. Importantly thoughts as well as other sensations can influence the sensory pain input to consciousness as well as the emotional coloring of the pain sensitization .
The term given for this modulation of pain impulses is the "gate control theory of pain". Thus thoughts (beliefs, fears, depression, anxiety, anger, helplessness etc,), as well as peripherally generated sensations, can both dampen or amplify pain. Indeed, in many chronic pain conditions (that lack any effective therapy for the sensory/pain component), a reduction of pain and the resulting suffering can only be effected by modulating the psychological aspects of pain. As the psychological contribution to pain varies enormously from patient to patient this approach has to be individualized.
However there are some general principles that are worth noting, There are important consequences of having pain that will not go away (as is the expected experience for most pain in most people). The unsettling realization that the problem may well be life-long generates a varied mix of emotions and behaviors that are often counterproductive to coping with a chronic problem. Many of these changes (which are partly reflex in origin) would be appropriate for dealing with acute self healing pain events, but become a liability when dealing with chronic pain.
The end result of chronic pain is often depressive illness, marital discord, vocational difficulties, chemical dependency, social withdrawal, sleep disorders, increasing fatigue, inappropriate beliefs and a radical alteration in their previous personality. Varying degrees of functional disability are a common accompaniment of chronic pain states. The reasons for dysfunction are multiple and vary from individual to individual. Pain often monopolizes attention (causing lack of focus on the task at hand).
It is usually associated with poor sleep (causing emotional fatigue). Movements may aggravate pain (causing a reluctance to engage in activity). Fear of activity often leads to deconditioning (which predisposes to muscle and tendon injuries and reduced stamina) .Pain causes stress, which may result in anxiety, depression and inappropriate behavior ( causing disability due to secondary psychological distress). The modern era of psychological imaging is providing an important new framework for understanding these "emotional" responses.
This discussion was given on 5/20/00 at 8:10 am.
References
1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SI, Fiechtner II, Franklin CM, Gatter RA, Hamaty D, Lessard I, Lichtbroun AS, Masi AT, McCain GA, Reynolds WI, Romano TI, Russell II, Sheon RP: The American College of Rheumatology 1990
criteria for the classification offibromyalgia: Report of the Multicenter Criteria Committee, Arth.Rheum. 33: 160- 172,1990
2, Bennett RM: The origin of myopain: An integrated hypothesis of focal muscle changes and sleep disturbance in patients with the fibromyalgia syndrome. I Musculoskeletal Pain 1:95-112, 1993
3, Armstrong RE, Warren GL, Warren IA: Mechanisms ofexercise-induced muscle fibre injury. Sports Med, 12:184- 207, 1991
4. Cohen ML, Quintner IL: Fibromyalgia syndrome, a problem of tautology. Lancet
342:906-909,1993
5. Merskey H, et al: Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain tenns. Seattle, IASP Press, 1994
6. Melzack R, Wall PO: Pain mechanisms: a new theory. Science 150:971-979,1965
7. Mendell LM, Wall PO: Response of single dorsal cord cells to peripheral cutaneous unmyelinated fibers. Nature 206:97-99,1965
8. Gracely RH LSBG: Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51:175-194,1997 ---
9. Kramis RC, Roberts WJ, Gillette RG: Non-nociceptive aspects of persistent musculoskeletal pain. J.Orthopedic and Sports Physical Therapy 24:255-267, 1996
10. Foreman RD, Kenashalo DR, Schmidt RF, Willis WD: Field potentials and excitation
of primate spinothalamic neurons in reponse to volleys in muscle afferents. J.Physiol.
286:215-231, 1979
II. Guieu R, Serratice G: Identifying the afferents involved in movement induced pain alleviation in man. Brain 115:1073-10789,1994
12. Beric A: Central pain:"New" syndromes and their evaluation. Muscle and Nerve16:1017-1024, 1993
13. Dubner R, Ruda MA: Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurol Sci 15:96-103,1992
14. Desbien NA. Wu A W.Alzola MS.Mueller-Rinzer N, Wenger NS Connors AF Lynn J. Phillips RS. Pain during hospitalization is asssociated with continued pain six months later in survivors of serious illness. 103,269-276. 1997
15. Wallace MS W ALJDM: Pain after breast surgery: a survey of 282 women. Pain 66: 195-205, 1996 i i
16. Buskila D, Neumann L, Vaisberg G, Alkalay D, Wolfe F: Increased rates offibromyalgia following c~cal spine injury. A controlled study of 161 cases of traumatic injury. Arthritis Rheum. 40:446-452, 1997 I
17. Dubner R: Hyperalgesia and expanded receptive fields. Pain 48:3-4, 1992 I
18. Dickenson AH, Sullivan AF: NMDA receptors and central hyperalgesic states. Pain 46:344-345, 1991 I
19. WoolfCJ, Thompson SW: The induction and maintenance of central sensitization is dependent on N-rhethyl-D- aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 44:293-299, 1991 i
20. Basbaum, A. I. Memories ofPain. 1,22-31.1996. I
21. Arnetz BB, Fjellner B: Psychological predictors of neuroendocrine responses to mental stress. J.Psyc~osom.Res. 30:297-305, 1986 i
22. Sastry BR: Substance P effects on spinal nociceptive neurones. Life Sci. 24:21781979 I
23. Coderre TJ, Katz J, Vaccarino AIJ, Melzack R: Contribution of central neuroplasticity to pathological pain: review of
clinical and experimental evidence. Pain 52:259-285, 1993
24. Lenz FA: Thalamic stimulation reproduces previously experienced pain. Nature Medicine I :910-913, 1995 25. Folz EL, White LEJ. Pain relieffonn frontal cingulotomy. Neurosurgery 19,89-100. 1962.
26. Devinsky 0, Morrell MJ Vogt BA. Contributions of the anterior cingulate to behaviour. Brain 118,279-306. 1995.
27. Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M: Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 63:225-236,1995
28. Jones and AKP .Pain, its perception, and imaging. IASP Newsletter May/june, 3-5. 1997.
29. McDermid Aj, Rollman GB, McCain GA: Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain 66:133-144, 1996
"
"
©2000 ProHealth, Inc.(ImmuneSupport.com)
All Rights Reserved.
|
|
|
|
|
