A National Conference at the Embassy Suites Resort, Scottsdale, AZ

3-5 March, 1995

Coordinated by the Dannemiller Memorial Education Foundation

of SanAntonio, TX

by John V Dommisse, MD, FRCP(C)

Nutritional & Metabolic Medicine & Psychiatry, LLC

Cambric Corporate Center, Tucson, Arizona 85718-5892

Nutritional, metabolic and psychiatric contributions to the prevention and amelioration of chronic pain will be presented in such a way that they should be able to be utilized later by the participants who attended the conference.

Chronic pain, which used to be regarded merely as a taboo symptom, is now seen as a disease-entity in its own right ¹ , controlled by an actual area of the brain, discovered by U of California researchers ² . It appears to be a good example of biopsychosocial causation in medicine ³

- therefore requiring treatment-responses in all 3 these areas. Its prevention can be tackled in primary, secondary and tertiary ways. Certain nutritional, metabolic and psychiatric manipulations can be very useful in preventing or ameliorating chronic pain; both by altering the biochemistry at the nerve-junctions in the brain, and by promoting a positive 'healing attitude' in the person suffering - or potentially suffering - from chronic pain. These 3 approaches will now be described, starting with the more traditional and familiar one of psychiatric intervention and then moving on to the exciting, new and potentially even more efficacious nutritional- and metabolic-medical approaches.

"It has been well-established that pain reflects complex linked neuroendocrine responses that go far beyond being merely a sensory alarm system. Accordingly, there may be significant medical consequences of inadequate recognition or treatment of pain." ⁴ .

"The pathophysiology of chronic pain is not well understood. To try to explain why pain may become long-lasting or chronic it is necessary to understand the plasticity of the neuronal circuits involved in nociception. It seems that mechanisms of learning and memory are involved in this process. Interactions between peptide and non-peptide neurotransmitters may be important. Other factors appear to be changes in gene induction and transcription, and cell injury and destruction as a result of excitation. Through these mechanisms, painful states may induce changes in the nervous system which lead to greater pain, making adequate prevention and treatment of nociceptive pain essential." ⁵

The treating person's attitude to the patient is important ⁶ ; the subjectivity of psychiatry can be a plus here. Psychiatry should usually be part of a team approach to the chronic pain patient ^7,8 . The following psychiatric approaches have been useful in the chronic-pain-patient-in-general, as well as in specific locations/ sites/ types of chronic pain:

(1) The use of antidepressants, which help both by alleviating associated depression and helplessness and by raising the pain threshold through raising the levels of certain neurotransmitters, especially serotonin ⁹ . (But not the benzodiazepines - they lower the pain-threshold). "Which came first: The pain or the depression?" is a chicken-and-egg argument; both conditions need to be addressed and treated for effective results ¹⁰ .

(2) The use of neuroleptics in neuralgic pain, esp. in combination with antidepressants ^11,12 . This useful treatment is often avoided because of the fear of a serious chronic side-effect, namely tardive dyskinesia. However, practitioners who utilize nutritional medicine in their practices do not need to be concerned as this side-effect does not occur in such practices; and, in cases in which it has already occurred (in non-nutritional practices), a certain combination of nutrients, in the correct dosages and with a few months of time, can almost always reverse it ¹³ .

(3) The delineation of the accompanying psychiatric symptoms in the chronic pain syndrome ¹⁴ . This can help medico-legally as well.

` (4) The assessment of the degree of depression in chronic pain patients ¹⁵ ; of the associated suicidal risk ¹⁶ ; and of the rationality of any 'realistic suicidal wishes' ¹⁷ .

(5) Assistance in distinguishing between organic and psychological illness..

(6) Management of narcotic/ addicting medications, especially in chronic-pain patients who have a history or tendency toward becoming addicted ¹⁸ .

(7) The application of knowledge of psychosomatic dynamics to pain syndromes ¹⁹.

(8) Case management and coordination of care by several different care-givers/ practitioners, e.g, in cases of chronic back pain ⁸.

(9) Psychiatrists can be useful in coordinating various coping strategies for the patient, in which he/ she may learn how to be more 'in control' and pro-active about their condition, join support-groups, elicit family-support, and make necessary lifestyle-changes.

(10) Relaxation and visual/ imagery techniques.

(11) The encouragement of creative expression to relieve chronic pain ²⁰ ; psychodrama; and meditational ²¹ / Ayurvedic medicine, art and music therapies, all of which can be health-promoting.

Examples of specific areas of chronic pain in which psychiatry can be helpful include:

(1) Psychiatrists can sometimes be the best practitioners to manage chronic headache cases ²² , including the use of lithium or calcium channel blockers ^23,24 .

(2) The loin pain and hematuria syndrome ²⁵ .

(3) Irritable bowel syndrome ²⁶ .

(4) The use of carbamazepine in trigeminal neuralgia and other pain syndromes ²⁷ .

(5) The use of divalproex sodium (Depakote) for pain associated with spasticity following spinal or head injuries ²⁸ : The drug acts by enhancing the GAGA-ergic neurones.

(6) As a member of the treatment-team in severely burned patients ⁷ .

(7) The use of hypnotherapy and bio-feedback for responsive pain-conditions like the reflex sympathetic dystrophy syndrome (RSDS) ²⁹ .

(8) Since there is a strong association between chronic musculo-skeletal pain and depression ³⁰ , and also between chronic abdominal pain and depression ³¹ , psychiatrists and antidepressant treatments have a direct application in these two particular types of chronic pain.

(9) Combatting the tendency for some cases to become 'professional or perpetual patients' (often Workmen's Compensation cases).

"Recent studies of central nervous system effects on pain and on its efferent modulation have created new theories and have led to direct clinical applications that may, in time, eclipse more-classical interventions. Thus electrical stimulation analgesia is presented as a paradigm of how basic science work has been applied clinically to produce some of the most exciting advances in recent years" ³² . Neuromodulators and neurotransmitters, like beta-endorphins, enkephalin, serotonin and other biogenic mono-amines, are being studied and found to be positively influenced by psychotropic, metabolic and nutritional interventions.

"The dorsal raphe nucleus (DRN) is an important nucleus in pain modulation. It has abundant 5HT (serotonin) and many other neurotransmitter neurons. Its vast fiber connections to other parts of the central nervous system provide a morphological basis for its pain-modulating function. Its descending projections, via the nucleus raphe magnus or directly, modulate the responses caused by noxious stimulation of the spinal dorsal horn neurons. In ascending projections it directly modulates the responses of pain-sensitive neurons in the thalamus. It can also be involved in analgesia-effects induced by the arcuate nucleus of the hypothalamus. Neurophysiologic and -pharmacologic results suggest that 5HT and ENKergic neurons in the DRN are pain-inhibitory and GABA-ergic neurons are the opposite." ³³ .

"Data from spinal microdialysis in decerebrated or anaesthetized animals indicate the possible importance of serotonin and substance-P in the dorsal horn for pain-inhibition by electrical spinal cord stimulation (SCS)" ³⁴ .

"SCS has been used as an effective method for managing pain and spasticity for over two decades. However, the mechanisms of these beneficial effects are largely unkown. Since neurotransmitters are likely to be involved, we examined the relationship between SCS and local segmental amino-acid release into the spinal cord extracellular space. Microdialysis was performed during continuous epidural SCS in animals subjected to ischemic spinal cord injury. Recovery of amino-acid neurotransmitters from stimulated injured animals was compared to that from a control-group. Evoked potentials from the cortex and spinal cord were recorded to ensure adequate stimulation and stable cord function. A significant increase in the concentrations of glycine and taurine was seen, before, during, and after 90 minutes of continuous stimulation and was independent of the degree of injury. Levels of the other putative amino-acid neurotransmitters were not significantly elevated. These results suggest that amelioration of pain or spasticity by epidural SCS may result from maintenance of post-injury elevation of glycine and taurine levels" ³⁵ .

By 'nutrition' I am referring mostly to the amino-acids, which are peptide parts of our protein foods; vitamins; and minerals. They also act against depression and insomnia, adding further to their beneficial effects in chronic pain patients, whose pain is aggravated by these two other conditions.

"It is now certain that some amino-acids in the diet can influence brain-activity by enhancing or reducing the metabolic rates of different neurotransmitters" ³⁶ .

"After long-term caloric restriction in Fischer-344 rats of both sexes, dopamine and 5HT content were decreased significantly in the caudate nucleus and the hypothalamus" ³⁷ .

"Dietary fluctuations in nutrient availability are factors in the regulation of brain function. Until recently, the prevailing view was that brain biochemistry and function were influenced by diet only when biochemical and clinical evidence of nutrient deficiency was present. It is now clear that the brain is sensitive and responsive to diet composition. Preliminary data show that variation in vitamin and mineral nutrient intakes over ranges that are considered to maintain normal nutritional status may impact brain chemistry, owing to their many coenzyme roles. Furthermore, the synthesis of at least 5 brain neurotransmitters, namely serotonin, the 2 catecholamines, acetylcholine, histamine and glycine, responds to dietary fluctuations in availability of their nutrient precursors, tryptophan, tyrosine, choline, histidine and threonine, respectively. Not only are these biochemical events altered by normal variations in diet composition, but considerable evidence now exists to show that the brain uses this information to regulate many functions ... under both normal and disease conditions" ³⁸ .

This is also the way in which nutritional factors control or influence neuromuscular dysfunction, as in myofascial pain syndromes such as temperomandibular joint pain syndrome ³⁹ . Fibromyalgia can be a feature of hypothyroidism, so, if subtle degrees of hypothyroidism are promptly diagnosed and treated, this would prevent another cause of chronic pain ⁴⁰ ..

"The use of dietary metabolic precursors to neurotransmitters in the management of chronic pain patients has received critical attention for several years. ... The serotonergic system serves as a useful model ... Oral L-tryptophan administration decreases the perception of pain, appearing to act synergistically with the enkephalins and endorphins. ... [There is] decreased pain perception, increased pain threshold, and improved sleep [which also helps the chronic pain patient's pain-perception]. From a therapeutic standpoint, dietary modification would appear to be attractive, due to its low economic basis, decreased risk of addiction and dependence [I would say no risk], as well as simplicity" ⁴¹ .

Several vitamins and minerals are required as essential enzymes in the production of these neurotransmitters from their precursors: e.g., folic acid ⁴² ; vitamin B6 ⁴³ ; and vitamin C ⁴⁴ . A deficiency of these vitamins and minerals can therefore cause a low pain-threshold, depression, insomnia, etc..

Tropamine^(R), a combination amino-acid, vitamin and mineral preparation that has been found to improve the neuromodulator deficits induced by cocaine-abuse ⁴⁵ , can be used to maximize neurotransmitter-levels in cases of chronic pain as well.

Spondylosis is a cause of chronic pain. Vitamin E has been shown to cure spondylosis, probably by its antioxidant effect ⁴⁶ .

Antioxidant nutrients have also been found very helpful in the healing of recurrent non-gallstone pancreatitis ⁴⁷ . Therefore it is likely that they would be helpful in chronic pain caused by other inflammatory conditions also.

D-PhenylAlanine (an amino-acid which blocks carboxypeptidase) has been found to enhance the effectiveness of acupuncture analgesia and acupuncture anesthesia in the treatment of low back pain and toothache by 16-35%, depending on the timing of its dosing ⁴⁸ .

Osteoporosis can be prevented and alleviated by paying attention to bone's multimineral requirements (not just calcium), and also to its requirements of proteins, and vitamins D and B12 ^49,50,51 .

Herpes zoster can be healed more quickly, and its pain can be diminished significantly, by vitamin B12 ^{52 - 55} .

References

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7. Watkins PN, et al: The role of the psychiatrist in the team treatment of the adult patient with burns. J BURN CARE REHABIL 13; 1 (Jan/Feb): 19-27, 1992

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