Biology 202
1999 Third Web Reports
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Pathways of Pain and Alternative Methods of Pain Relief

Patricia Kinser

Have you ever wondered why when you stub your toe on the chair in the living room, it helps tremendously to yell out an expletive or two and vigorously rub the area? I may not be able to discuss the basis for such language in this paper, but we will explore the analgesic response to rubbing that toe, in addition to the mechanism of pain and alternative treatments such as acupuncture and transcutaneous electrical nerve stimulation.

In the two previous papers for this class I have chosen to focus upon the inherent power of the brain in relation to healing. Studies of the placebo effect and psychoneuroimmunology have helped us gain insight into the nervous system's relationship with the immune system, the endocrine system, and others. Alternative therapies such as hypnosis, relaxation/ meditation, and humor have been discussed in association with this relationship. I feel that my exploration of the brain and alternative healing would not be complete without an investigation of the processing of pain and the role of acupuncture and touch in pain relief.

What exactly is pain? According to Webster's dictionary, pain is "physical suffering typically from injury or illness; a distressing sensation in a part of the body; severe mental or emotional distress". Most everyone reading this paper has experienced some form of physical pain at some point during their lives; most everyone has even experienced the common daily pains such as stubbing our toe as we walk through the living room, accidentally biting our tongue as we chew, and having the afternoon headache after a long day of work. No matter the fact that it is unpleasant, pain has a very important role in telling the body that something is not right and leading to behavior that will remove the body from a source of potential injury. Imagine if we could not experience pain. We would not be able to change our behavior in any way when touching the burning hot dish in the oven, resulting in potentially serious burns. We could not recognize that perhaps we twisted an ankle when walking down the stairs, thus continued walking on that foot would exacerbate the injury to the point of not being able to walk at all. Indeed, pain is not pleasant, but in many cases it is an important way for our nervous system to learn from and react to the environment.

Mechanisms of Pain

What is the mechanism for pain sensation and response? Pain is a sensation characterized by unpleasant perceptual and emotional experiences that trigger various autonomic, psychological, and somatomotor responses. It is believed that this sensation consists basically of two types: 1) rapidly conducted action potentials carried by large- diameter myelinated axons, resulting in the sensation of sharp, well-localized pricking or cutting pain; 2) more slowly propagated action potentials carried by smaller, less heavily myelinated axons, resulting in the sensation of burning or aching pain (1). Variations in pain sensation result from the differences in integration of action potentials from pain receptors and the mechanisms by which pain receptors are stimulated. Usually, pain information originates in the periphery, for example, stubbing the toe. The change in tissue results in the release of substances from neurons adjacent to that tissue, possibly neuropeptides, serotonin, histamine, proteolytic enzymes, and prostaglandins, that activate pain fibers in the skin (2). It is believed that pain receptors are activated by the same stimuli that affect tactile and mechanoreceptors (1), since there may not be any specialized receptors or fibers that respond to noxious stimulation. Action potentials from tactile receptors probably help localize the source of pain and monitor changes in stimuli (1). This may explain why superficial pain is highly localized and perceived as sharp, since there is a high concentration of tactile receptors in the skin which are stimulated simultaneously as the pain receptors. Deep or visceral pain is often perceived as diffuse due to the absence of many mechanoreceptors in more deeper structures (1). Certain receptors have been identified which respond solely to noxious stimulation, called nociceptors. It has become possible to record the discharge frequency of these fibers and directly correlate the activity with the perceived intensity of pain (3).

The exact form of stimulus- response function is not known, but I we will look at some of the commonly accepted explanations. Concurrent activity in nociceptive and non-nociceptive fibers can strongly affect the perceived intensity of pain, demonstrating that convergence of afferent activity onto neurons in the spinal cord is key for pain mediation (3). Afferent fibers carry the nociceptive information from the periphery to the dorsal horn of the spinal cord. Several tracts in the spinal cord ascend to the brain, carrying information about peripheral nociception. Most pain researchers agree (1,2,3,4,5...) that pain experience is multidimensional, involving 1) a sensory- discriminative component, represented by the ability to identify the stimulus according to space, time, and intensity; 2) a hedonic component, where the unpleasant qualities of pain are experienced; and 3) a cognitive component, reflecting the ability to evaluate the significance of the pain in terms of its implications for survival and threat to well-being. These three components are most likely mediated by anatomically and functionally distinct neuronal systems which interact together and are most likely located in a variety of structures in the forebrain (3).

Recently, the positron emission tomography (PET) has been used to study cerebral blood flow in identifying regions with increased neuronal activity during experimentally induced pain. A variety of structures are shown to be associated with pain mediation and the three different components of pain. The sensorimotor cortex and the contralateral central posterior thalamus may be involved with the first component, discrimination, of pain; pre-motor areas and regions with connections with the limbic system are associated with the hedonic component of pain; prefrontal cortical areas may be involved with pain- related cognitive function (3).

The brain can control the flow of pain signals in a variety of ways. Of a couple of theories, two are most highly accepted. The first is designated as the Gate Control Theory where primary neurons of the dorsal column- medial lemniscal system have branches which synapse with association neurons in the posterior horn of the spinal cord. These association neurons can have an inhibitory effect on the secondary neurons of the lateral spinothalamic tract, which is one of the most important pain pathways ascending the spinal cord and terminating in the thalamus (1). Thus, pain action potentials traveling the spinothalamic tract can be suppressed by action potentials from the dorsal column- medial lemniscal system, whose neurons act as a "gate". Increased activity in the dorsal column- medial lemniscal system tends to close the gate, reducing pain action potentials transmitted in the spinothalamic tract, thus reducing pain experienced by the patient (1). As we will see later, this theory has important implications for the physiological basis of methods used to reduce intensity of chronic pain, such as acupuncture. It has been suggested that L-fibers (large diameter fibers) , which are responsible for closing the gate, are connected to higher brain processes of cognition, experience, and culture (4). This connection, too, has implications for the efficacy of acupuncture.

The second method for the brain's control of pain is the incorporation of endogenous opioids, such as endorphins, in pain circuitry. In a sense, these chemicals act as the brain's own morphine. Experiments have shown that excitation of periaqueductal gray neurons results in stimulation of neurons in the medulla by axons containing endorphins (2). The medulla neurons have serotonin- containing axons which inhibit spinal cord neurons transmitting information from the periphery. Thus, pain action potentials are blocked in the spinal cord. It is important to note that tactile stimulation activates endorphin production.

Now, perhaps, we have a greater insight into the mechanism of pain sensation that comes from peripheral noxious stimulation. Yet, what about the pains that are the most annoying, most debilitating in our daily lives- headaches and other chronic pains such as arthritis and back pain? About 40 million Americans have chronic headaches and approximately 80 percent of Americans will experience lower back pain in their lifetimes (5). The annual cost of pain medications is more than $4 billion and close to 60-80 percent of patients are not satisfied with their pain care (5). Knowledge of the exact mechanisms responsible for headaches leaves much to be desired. Many theories are currently established and under review, including ideas such as: the widening or narrowing of extra- and intracranial arteries, impaired autoregulation of normal vasomotor mechanisms, neuronal trigger mechanism in the pons, platelet aggregation, inflammation in or about any pain- sensitive structures of the head, tumors around nerves containing pain- afferent fibers, and others (6). A variety of chemical neurotransmitters have been implicated, including acetyl-choline, norepinephrine, serotonin, neurotensin, vasoactive intestinal polypepetide, and adenosine triphosphate (6). In order to be able to effectively treat headaches and other types of chronic pain, further research is presently occurring to determine the exact mechanisms for pain signaling. Chronic pain is very debilitating and patients may often become dependent upon drugs, which suggests that studying pain mechanisms and finding alternative therapies, such as acupuncture, for effective relief of pain is necessary.

One of the most interesting and important things about perceived pain is that it does not correlate directly to events at the periphery of the body, i.e. there is no straightforward relationship between receptor events and pain perception. One example of this is "phantom pain" which occurs in a part of one's body that has been amputated. Another example is that the intensity of pain is the balance of activity in a number of somatosensory pathways, rather than simply the activity of the nociceptive pathway. Finally, a last example is that release of endorphins is partly responsible for suppression of pain, especially in certain contexts such as childbirth and athletic competitions (7).

Acupuncture and TENS as Pain Treatment

Due to the fact that most everyone experiences the unpleasant sensation of pain during their lifetimes, it is not surprising that there are a huge variety of analgesic treatments. One such treatment is acupuncture, which originates as an enduring component of health care in China. Acupuncture involves stimulation of certain points by penetration of the skin by thin, solid needles which are manipulated manually or by electrical stimulation. The relationship between acupuncture points and the nervous system is demonstrated by the following statistic: out of 324 points studied, 99% were within .5mm from innervation of cranial spinal nerves, 96% were related to superficial cutaneous nerves, and 86% were beside an artery (9). Thus far, the National Institutes of Health (NIH) and the World Health Organization have identified a variety of medical conditions which could benefit from acupuncture, including nausea and vomiting, pain, drug/alcohol/tobacco addictions, pulmonary problems, and stroke (8).

The Gate Control theory and the role of endogenous opioids in pain mediation may both explain the analgesic effects of acupuncture. Action potentials initiated by acupuncture procedures may inhibit the action potentials in neurons of the spinothalamic tract which transmit pain signals upward in the spinal cord (1). Also, as we have seen, a summation of activity in somatosensory pathways in addition to nociceptive pathways is reflected in intensity of pain (7). If this is the case, then perhaps stimuli from acupuncture needles accompanies nociceptive activity, tempering pain perception.

When opioid antagonists, such as nalozone hydrochloride, are administered prior to acupuncture treatment, the pain control effects are reduced or blocked (8). This suggests that opioid peptides are released during acupuncture, explaining the analgesic effect. Stimulation by acupuncture may also activate the hypothalamus and pituitary gland, alter the section of neurotransmitters and neurohormones, change blood flow regulation, and positively affect the immune system (8).

Closely related to acupuncture, transcutaneous electrical nerve stimulation (TENS) is the delivery of electric pulses through electrodes attached to the skin, exciting nerves near the region that the patient reports pain. Some common uses of TENS treatment are acute and chronic pain, post operative pain, labor and delivery, headaches, arthritis, and others (10). As in acupuncture, the Gate Control theory and the Endorphin Release theory, as well as others illustrated later, explain how TENS decreases or eliminates pain, without danger of dependence or adverse side effects. In a study of the effect of TENS vs. naproxen (an orally administered pain medication) on menstrual pain, it was found that high- intensity TENS is an effective and safe form of therapy for pain (12). Especially when the pain is believed to be secondary to local ischemia (Endnote 1) as opposed to neurogenic or musculoskeletal origin, success rate was considered to be around 90 percent, with onset of pain relief around 60 seconds (12). This fact shows us that there may be other mechanisms involved other than direct suppression of nociceptive activity in spinal nerve fibers, as in the Gate Control theory. These results involving pain and ischemia also are positive when considering headache relief. As a final possible explanation for the efficacy of TENS, Thomas Lundeberg, from the Dept. of Physiology and Pharmacology at the Karolinska Institute in Sweden, found that "electrical stimulation is followed by a decrease in the excitatory amino acids glutamate and aspartate in the dorsal horn, which is mediated by a GABAergic mechanism" (11). In other words, inhibition of nociceptive neurons at the spinal cord level may involve GABA, as evidenced by counteraction of inhibition by GABA antagonists. He notes, however, that knowledge about the mechanisms underlying the effects of TENS and acupuncture is limited and further research is necessary to discover full potential of such treatment.

Stimulation of the skin via acupuncture or TENS has been shown to have analgesic effects for acute and chronic pain. The implication of evidence for the positive effects of these treatments is very important. Patients suffering from pain that is not being treated effectively or patients who have found themselves too dependent upon drugs for pain relief could potentially benefit greatly from these alternativepain treatment therapies. Indeed, intensive research is required for further understanding of both the mechanisms of pain and the exact effects of these treatments. What we do know, however, as far as the mechanism for the treatment of pain by these methods demonstrates the importance of touch in pain relief. As mentioned at the beginning of the paper, understanding pain pathways is important not only for treatment of chronic pain but also for a basic knowledge of why shouting expletives and rubbing our foot helps the pain to go away.

WWW Sources

1) Pain

2)Rosenzweig, Leiman, Breedlove. "Biological Psychology". Sinauer Associates, Inc.: Sunderland, MA, 1996.

3) Lexis-Nexis search: Casey, Kenneth L. "Match and Mismatch: Identifying the Neuronal Determinants of Pain". Annals of Internal Medicine: Vol. 124(11), June 1, 1996, p. 995-998.

4) Pain Perception

5) Chronic Pain

6) Mechanisms of Headaches

7) Pain Pathways

8) Lexis-Nexis search: NIH Consensus Conference. "Acupuncture". JAMA: Vol. 280(17), Nov. 4, 1998, p. 1518-1524.

9) Scientific Basis of Acupuncture

10) TENS

11) Lexis-Nexis search: Lundenberg, Thomas. "Electrical stimulation techniques". The Lancet: Vol. 348(9043), Dec. 21/28, 1996, p. 1672-1673.

12) Lexis-Nexis search: Milsom, Hedner, Mannheimer. "A Comparative Study of the Effect of High-Intensity Transcutaneous Nerve Stimulation and Oral Naproxen." Am. J. of Obs. and Gyn.: Vol. 170(1), Jan. 1994, 0. 123-129.

Endnotes

1 Ischemia is a local deficiency of blood supply produced by basoconstriction or local obstacles to the arterial flow.


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This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.

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