“The two enemies of human happiness are pain and boredom.” -Arthur Schopenhauer (1788-1860)
pain n.: usually localized physical suffering associated with bodily disorder. -Webster’s New Collegiate Dictionary
Pain is the opposite of pleasure. Each involves different neurobiology.
Neuroanatomically, pleasure involves the ventral tegmental area and nucleus acumbens, neither of which subserves pain. Neurochemically, pleasure involves dopamine, which does not subserve pain directly. The dopamine-mediated signal cascades from the limbic system to the cortex.
Subserving the emotion of pain is nociception; that is, the production of afferent, neuronal signals created by depolarizing the membranes of projections from neurons in the dorsal ganglia just outside the spinal cord and, thereby, activating their voltage-sensitive sodium channels; transmitting those signals via axons to neurons in the dorsal horn of the spinal cord; then having the signals ascend via the spinothalamic tract to the thalamus in the brain. The thalamus acts as a relaying station among various parts of the brain. In animals with more highly developed nervous systems, the thalamus relays the signal to the limbic system, which, in turn, relays it to the neocortex. The specific, responding characteristics of primary, afferent neurons reflect their specific receptors and channels.
Nociceptive stimulation elicits an immediate response of withdrawal to escape the stimulus eliciting the nociceptive signal. Nociception is not pain. Neuroanatomically, it involves Aδ and C fibers. Excitation also may involve non-nociceptive afferent, Aβ fibers. Nociceptive stimulation begins with the release of glutamate and substance P. Initially, glutamate binds to only receptors for α-amino-3-hydroxy-5-methyl-4-isoxaloproprionic acid; eventually, however, glutamate can begin binding to receptors for N-methyl-D-aspartate, which can elicit hyperalgesia lasting from days to months or longer; thereby, an acute response can become chronic.
Pain comes in two, basic forms — acute and chronic. Each involves different neurobiology.
Acute pain activates the anterior cingulate gyrus and the posterior insula, among other sites. It directly activates the frontal cortex little, if at all.
There appear to be two, basic kinds of acute pain — 1) spontaneous, high intensity pain; and 2) spontaneous, increasing pain. In individuals with underlying chronic pain, additional acute pain can activate the medial prefrontal cortex. Of note, this cortical area subserves emotional self-representation and self-regulation; thus, chronic pain involves areas of the forebrain subserving emotions, thereby, eliciting emotional discomfort. Also of note, activity in the insula itself does not appear connected to emotions.
Chronic pain represents a serious medical condition deserving proper, medical treatment. It represents negative strain that up-regulates cortico-trophic regulating hormone. One consequence of such up-regulation is suppression of brain-derived neurotrophic factor. Neuroanatomical changes associated with chronic pain resemble those with chronic depression; for example, enlarging ventricles and volume loss especially in the hipocampal and para-hippocampal areas.
Chronic pain activates release of cytokines and other inflammatory agents. The overall effect can be activated microglia with loss of cellular integrity and apoptosis; i.e., disintegration of cells into membrane-bound particles then phagocytosed. It can induce indoleamine 2,3-dioxygenase that prevents the conversion to serotonin of its precursor. Furthermore, it can activate receptors for N-methyl-D-aspartate with the consequent release of glutamate and its further exitotoxicity; inflammation; and apoptosis. This cascade of neurochemicals is similar to that found in depression.
In fact, depression and chronic pain are closely allied enemies of the patient. Approximately 30% of patients with chronic pain suffer associated clinical depression. Approximately 20% experience suicidal ideation with the rate of suicide being three times higher than that among the general population.
As occurs with depression, chronic pain often is associated with sleeping disturbances. Such disturbances can increase the magnitude of pain experienced during waking hours.
As many as 30% of individuals experiencing an acute pain find the pain becoming chronic. The mechanisms appear complex and not well-understood.
One mechanism appears to involve central sensitization. A majority of patients with neuropathic pain (i.e., pain from pathology in the nervous system itself) seem to exhibit this phenomenon. Central sensitization is linked to several, different neurotransmitters although glutamate appears to be a primary culprit. Central sensitization appears to be a function of duration, so the longer the pain, the longer the pain — early, aggressive treatment very well may alleviate this pernicious phenomenon.
A second mechanism, associated with central sensitization, is temporal summation involving Aδ and Aβ fibers. Temporal summation is the consequence of repeated stimulation of an affected area; thereby, increasing the experiencing of pain.
A third mechanism involves the neurological inhibitory system. Nociception and pain also involve descending, inhibitory pathways from the periäqueductal area in the brainstem to the lamina of the dorsal horn in the spinal cord. Neurochemically, inhibition is subserved primarily by norepinephrine and serotonin with some input from dopamine and endocannabinoids activating endogenous opioid receptors adjacent to ascending fibers therein; thereby, dampening the nociceptive signal to the brain from below. The involvement of norepinephrine and serotonin may explain the unusually rapid, analgesic effect in chronic pain of antidepressant medication, especially amitryptilene, in dosages too low to treat depression.
A fourth mechanism also involves inhibition. As chronic pain increases in duration, activity in the medial prefrontal cortex increases. Addition of acute pain can activate further the medial prefrontal cortex while deäctivating the dorsolateral prefrontal cortex. This latter structure dampens chronic pain by inhibiting activity between the thalmus and midbrain, rendering pain less emotional. An increasing duration of chronic pain actually shrinks gray matter in the dorsolateral prefrontal cortex, which might be reversed by trans-cranial magnetic stimulation. Curiously, increasing duration may increase gray matter in other regions of the brain.
The first choice in treatment of chronic pain is to eliminate the offending stressor. Unfortunately, doing so is often impossible. Attempts, such as multiple spinal surgeries, can do more harm than good because healing involves scarring, and scars contract; thereby, deforming surrounding structures. Put simply, the back doesn’t like to be cut.
Different causes of chronic pain deserve different therapeutic approaches. One common choice for the unsuspecting is chiropractic. Chiropractors are not medical doctors. They are not physicians although, as a consequence of political lobbying, some states allow them to wrap themselves in the camouflage of “chiropractic physician”.
Chiropratic was invented by a charlatan named D. D. Palmer (1845-1913) in the late 19th-century. He proposed a theory that disease was the consequence of poor alignment of the vertebrae, which could be relieved by manipulation. He was wrong as are his followers today. Hemorrhoids, for example, are one of the most common of human maladies; yet, the nerves subserving the area emanate from the sacrum, which is fused.
Subsequent to Palmer, chiropractors employed electronic devices resembling vertical pinball-machines ostensibly to diagnose disease with a “sensor” held in the hand. Their doing so constituted obvious chicanery that prevented people from seeking proper medical treatment.
Even today, Palmer’s followers make fanciful claims while applying procedures of questionable value but unquestionable risk. Adverse consequences, including death from dissection of the vertebral artery (See, for example, Chen, WL, et al: “Vertebral artery dissection and cerebellar infarction following chiropractic manipulation”. Emergency Medicine Journal 23: e1, 2006.) are commonplace, reportedly at a rate of 30% (See, for example, Hurwitz, EL, et al: “Frequency and clinical predictors of adverse reactions to chiropractic care in the UCLA neck pain study.” Spine 30:1477, 2005.).
To begin, some words about opiates. Cultivation of the poppy began around 3400 BC in lower Mesopotamia. The Sumerians referred to it as the “joy plant”. Morphine, the active ingredient in opium, was not identified until the early part of the 19th-century.
Sumerians notwithstanding, opiates should be employed to relieve chronic pain only as a last resort. Not only can they be addicting although some patients report dysphoria rather than euphoria, they actually can exacerbate chronic pain by inducing hyperalgesia probably related to N-methyl-D-aspartate and protein kinase. If employed, their use should be continual not as needed and at the minimal, effective level — best <60mg. of morphine-equivalent. Methadone should be avoided. The good news, however, is that outright addiction to “drugs of abuse” is no higher than among the general population; which may bear witness to the negative strains elicited by modern society, leading to a recent, general increase in abuse of increasingly potent street-heroin..
Different stressors may require different treatments. Several treatments of proven value are available. Unfortunately, always adhering to the guidelines of the Food and Drug Administration may prevent patients from receiving optimal medication.
For the still-problematic diagnosis of fibromyalgia, recommended medications include duloxetine, a serotonin-norepinephrine uptake inhibitor, and pregabalin, an anti-epileptic that diminishes release of glutamate via blockade of a2δ subunit of voltage-sensitive, calcium channels.
For cluster-headaches, lithium appears helpful. Psychiatrically, it also is used as a medication to control mania among manic-depressives.
For migraine headaches, a newer, sometimes helpful approach is the use ziprasidone. Psychiatrically, it is used to treat schizophrenia.
As for chronic back pain, it represents a heavy burden on its sufferers clinically and upon society economically. There is no single, effective treatment. Perhaps, the most effective medication is an old one — amitryptilene begun at very low dosage that is increased slowly as tolerated. Other medications often recommended are duloxetine, nortryptilene, and venlafaxine.
A few words about selective serotonin uptake inhibitors (SSRIs). In the descending fibers of the spinal cord, serotonin both may inhibit and facilitate. Accordingly, medications that inhibit the reüptake of both serotonin and norepinephrine (SNRIs) may prove more effective in treating chronic pain.
Furthermore, increasing levels of serotonin have their own consequences; e.g., cognitive dysfunction especially impairment of memory, fatigue, obesity, sexual dysfunction, and somnolence. SSRIs are no more effective and probably less effective than tricyclics (or even MAOIs) and, for males especially, less well tolerated. If SSRIs are prescribed, it should be noted that NSAIDs such as ibuprophen may anatgonize the actions of SSRIs; possibly via p11, a small protein implicated in the actions of cytokines.
Physical treatments other than pharmacological depend upon diagnosis made by a physician. For ailments involving the musculo-skeletal system, such as chronic back pain, physical therapy prescribed by a physician, especially a physiatrist, can bring substantial relief. Often, supplementing physical therapy with nutritional counselling, occupational therapy, and recreational therapy can add to the effectiveness.
As for any medical disorder for which there exists no single, effective treatment, a variety of problematic treatments exist for chronic, musculo-skeletal pain. These include epidural injections of steroids, radio-based ablation, sympathetic blockade, and spinal cord stimulation.
For ailments not involving the musculo-skeletal system, treatment must be tailored to the individual and to the disorder. Other than direct medical treatment, often there is little to offer except so-called supportive groups, which unfortunately can amount to the blind leading the blind.
Mental treatments remain controversial. There is some suggestion that meditation or even Relaxation Procedure can be helpful.
As for psychiatric treatment other than medication or counselling by so-called therapists, many of whom are of dubious qualifications, the picture is bleak. Few clinical psychologists even at the doctoral level and fewer psychiatrists have knowledge, training, and experience in Biobehavioral Science and Technology. In their stead, “therapists” offer that which has become popular — so-called cognitive-behavioral therapy (“CBT”); which, in terms of its basic model, often amounts to psychoanalytically-oriented therapy without the charm. For a presentation of a truly biobehavioral model and a discussion of “CBT”, see Part Two of the semi-fictional novel, Inescapable Consequences.
“ When sorrows come, they come not single spies but in battalions.” -William Shakespeare from Hamlet (Act IV, Scene V)
Pain and sorrow are familiar enemies attacking mankind since time immemorial. With the birth of science, as such, in the mid-19th-century, we have come far in reducing the pain and sorrow of disease and trauma. Even so, many continue to suffer the discomfort and sorrow of chronic pain and its associated infirmities.
As described, chronic pain and depression utilize many of the same anatomical, physiological, and chemical structures. Untreated medically, the toll that they exact can be ruinous — mentally, physically, economically, and socially.
Making a bad situation worse, so-called healthcare plans deny optimal treatment — treatment that can combat effectively chronic pain and its attendant sorrows [See Moss GR and and James CR: Pilot study of a behavioral medicine program in a community hospital setting. Journal of Behavior Therapy & Experimental Psychiatry 17: 3-9 (1986).]. These plans, initially demanded by the federal government and operated by profiteers, have displaced real medical insurance in favor of “managed care” that actually is “managed cost” (See Healthcare Reform D.O.A. now out of print but available used.).
Listen not to the governmentally-inspired propaganda. Real medical insurance no longer exists.
Who suffers? To some substantial extent, physicians; to a much greater extent, patients. We are witnessing the Sovietization of American medicine. In the near future, most Americans will be treated by “Dr. Nurse” instead of “Doctor Doctor”. Nurses and Physicians’ Assistants are not physicians. They are para-medical personnel not medical personnel. In this context, consider the future plight of those suffering the sorrows of chronic pain.
Is there a scientifically-based, scientifically-driven alternative? Yes. (See Chapter 17 of Inescapable Consequences.) Shall we employ it? Not likely.
In order to comment, you must be registered with WordPress.