The Percept of Pain: Where does it come from?

Biology 202
2002 Second Paper
On Serendip

The Percept of Pain: Where does it come from?

Raquel Deering

In class we have discussed the concept of pain, concluding that a conflict between what the brain anticipates occurring and what actually occurs has the potential to cause the perception of pain. Furthermore, it was suggested that genetics might have a role in the experience of pain, particularly when applied to the discussion of phantom limb pain. However, I found these inferences a bit unsatisfying and walked away with more questions than answers. Where does chronic pain come into the picture? Why is a stimulus that is painful for one person not for another? And the question that puzzled me the most: how, from a neurobiological perspective, can an individual experience pain in her arm if she was born without one?

Pain, a component of the somatosensory system, is defined by the International Association for the Study of Pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" (1). The perception of pain serves as a defense system to maintain homeostasis, warning of injury that should be avoided and/or treated. Injured limbs actually inhibit voluntary movement to promote necessary healing processed (2). So essential is the painful response that those individuals born with congenital pain insensitivity do not react to pain, often resulting in severe, permanent tissue damage, and even premature death.

A crucial concept in the definition of pain is that it is indeed a perception, therefore involving the brain's rumination and elaboration on corresponding input. This may be paralleled to another sensory perception, vision. Although the optic nerve head should cause a "hole" in an individual's sight, no discontinuity is appreciated; the brain evaluates the environment surrounding the hole and produces the most appropriate continuous image. Likewise, there is the possibility that the nervous system's influence can change aspects of pain.

What is happening during a painful experience? Two classes of pain have been delineated: nociceptive pain and neuropathic pain. The latter division involves only direct injury to nerves in both the central and peripheral nervous systems. Tissues containing specialized sensory receptors, called nociceptors, are activated by noxious stimuli and have been discovered to exist in almost all multicellular animals on Earth, as well as in some bacteria (2). Nociceptors are most abundant in superficial areas of the skin, joint capsules, inside the periostea of bones, and around vessel walls (3).

Although nociceptors are involved with pain perception, stimulation of a nociceptor does not invariably result in a painful response. Unlike other sensory receptors, nociceptors become increasingly sensitive with continued stimulation. Damaged tissue releases prostaglandins and leukotrienes, chemicals that sensitize nociceptors (4). These nociceptors respond to stimuli that would not normally be interpreted as painful (this is sometimes called allodonia). For example, sunburn pain is exacerbated by a gentle touch or breeze due to the hyperactivity of the nociceptors. Aspirin and similar drugs reduce sensitization by inhibiting the production of prostaglandins (5).

Three types of nociceptors have been classified: A delta (I and II), medium-diameter cell bodies with lightly myelinated axons, and C fibers that have small-diameter cell bodies and non-myelinated axons (4). The myelinated A delta fibers conduct impulses faster and thus communicate with the brain sooner than the C fibers. Further categorization of identifies nociceptors as mechanical, thermal, and polymodal. Mechanical nociceptors involve the activation of A delta conducting at 5-30m/s fibers during the experience of intensive pressure. Likewise, thermal nociceptors are activated by extreme hot or cold temperatures (>45°C or <5°C), and also involve thinly myelinated A delta fibers. Polymodal nociceptors are activated by high intensity mechanical, chemical, and thermal stimuli, involving non-myelinated C fibers. All classes of nociceptors are present on skin and tissues and work together in forming the pain response. For example, one may initially experience a feeling of "sharp" pain when hitting their thumb with a hammer, proceeded by a prolonged "aching." The first pain occurs when A delta fibers transmit information from mechanical and thermal nociceptors to the brain. C fibers transmitting polymodal nociceptors are responsible for the later, prolonged aching experience (6).

A delta and C fibers travel through the pain gate and synapse with other nerve fibers in the marginal layer (lamina I) and the substantia gelatinosa (lamina II) of the superficial dorsal horn (6). The fibers then release a neurotransmitter, substance P, into the synaptic cleft, sending an impulse up to the thalamus. The thalamus then sends two signals; one to the cerebral cortex and one back to the original location of pain to inhibit nociceptors from transmitting further unnecessary pain impulses. The signaled cerebral cortex considers the tissue damage and transmits messages to both the limbic system and the autonomic nervous system (ANS). The limbic system functions to increase or subdue pain by controlling the individual's emotional responses. Blood flow, pulse rate, and breathing are moderated by the ANS, therefore ANS assistance helps to provide an ideal environment for damaged tissue restoration (4).

Chemical messages transmitted by hormones also influence conduction of pain signals to the brain. The previously mentioned prostaglandins increase the frequency of impulses in addition to sensitizing nociceptor nerve endings. Substance P stimulates nociceptors at the site of injury to intensify the incidence of pain sensation. For pain reduction, the hormones Serotonin and Norepinephrine are released to promote the liberation of endorphins by nociceptors (4). Thus, by the release of hormones both an individual's pain experience and perception are altered. This leaves additional room for variation in such experience among people.

As mentioned above, A delta and C fibers travel through the pain gate before any further signal transmission occurs. The gate control theory of pain was presented in 1965 by Melzak and Wall, and has crucial implications for the painful experience. The "pain gate" is positioned in the dorsal horn at the base of the spinal cord. It serves to screen nerve impulses; the majority of impulses from a certain class of fiber are permitted to travel through the spinal cord and to the brain. For example, if touch/pressure impulses (A delta I fibers) outnumber painful impulses (A delta II fibers), then only the touch/pressure impulses are received by the brain (7). This is why intensely massaging a pain site tends to reduce the perception of pain. Acupuncture works similarly. By applying strong pressure to a very localized site, pain signals will not successfully pass through the pain gate and hence little or no pain is perceived by the individual (4).

Having explored the conventional explanation for pain, I was more comfortable with how variations among persons can exist in their perception of pain. However, the idea of phantom limb pain still eluded me. Under the conventional pain theories, phantom pain is explained by central sensitization of dorsal horn neurons. Some noxious conditions are severe and persistent enough to cause prolonged stimulation of C fibers, also eliciting a progressively more intense response from the dorsal horn neurons. Long-term changes in dorsal horn neurons result, altering the biochemical properties and excitability of the neurons (3). Changes at the molecular level are thought to involve modification of the genetic transcription of neurotransmitters and receptors (8). These alterations are responsible for spontaneous pain events evidenced by amputees. It is proposed that the insult of the surgical procedure triggered a central sensitization state in an individual's dorsal horn nerves. Also, chronic pain may be attributed to a similar process of neuronal hypersensitivity (3). One study on phantom limb pain examined the MEG map differences from a cohort of amputees. It was concluded that an appreciable degree of somatosensory cortical reorganization was evident and should be considered (9).

Although this explanation sounds feasible, it does not explain why individuals having been born missing a limb experience phantom pain. The nervous system is not responding to, or has been altered by, a devastating surgical procedure. Yet the individual relates not only pain and movement experiences, but also acknowledges a persistent sense of spatial position of the missing limb (7).

I discovered a paper written by Ronald Melzak, one of the "pain gate theory" formulators. He was similarly frustrated by the existing explanations for phantom pain and explored the possibility of an entirely revised system for regulation by the nervous system. Other neurological research has not able to assign the perception of pain to a specific part of the brain. In fact, so many sensory and cognitive processes are involved in perception that it is almost irrefutable that the majority of the nervous system must be related to the full perceptual experience. Using data from the evaluations of paraplegics with spinal cord sections and individuals suffering from phantom pain, Melzak concluded that the body we feel (the "body-self" identity) and the phantom limb are regulated by the same neural pathways. Furthermore, the qualities we associate with the body, including pain, are also experienced in the absence of sensory inputs from the body (7). Melzak is proposing that the origins for patterns of basic experiences are generated in neural networks in the brain; these patterns are intrinsic to the brain. Therefore, stimuli do not cause these pre-existing pattern generators, but rather initiate the activation of them. It would not be necessary to possess a body to experience one.

Melzak coins the term "neuromatrix" to explain a possible mechanism for pattern generation and the nervous system's interaction with the environment. The neuromatrix refers to a function that is continuously aware of the entire body, producing a feeling of unity. Although millions of nerve impulses are hitting the nervous system each moment, it is essential for the sense of body to be maintained. Details from inputs are integrated into the neuromatrix as they arrive, allowing for continual revision, and inputs are analyzed and synthesized to produce appropriate responses. Using this logic, it can be inferred that commands originate in the brain and actually produce experiences. This may explain why amputees suffer genuine fatigue from the experience of persistent bicycling movements, or amputees relate the feeling of pain from clenching an imaginary fist (7). Unfortunately, there exists no delineated cure from chronic pain and phantom pain; the neuromatrix involves many parts of the brain and it is possible that these pattern generators cannot be mechanically altered without causing disturbance of deeper levels of perception.

The implication that a brain can generate perceptual experience without first acquiring input is provocative to say the least. However, the same phenomenon has been accepted when discussing the absence of a blind spot in vision. Can we attribute enough authority to the brain to suggest that it controls our experiences? Should pain now only be defined in terms of perception and not physical injury? It think this theory should be explored and may be useful in understanding the human perception of reality in general. Although typically cynical about notions that are not physiologically observable, I am surprisingly excited by the idea of a neuromatrix and look forward to rethinking my pervious understandings of the nervous system's workings. It may be interesting to see how the I-function is involved with this process and why pain treatments such as biofeedback have been known to produce positive results.

References

1) Journal of Physiology , An article on the Journal of Physiology website.

2)Chronic Pain Solutions, A paper on the etiology and treatment of pain.

3) Kandel, Schwartz, and Jessel. Principles of Neural Science, 4th Edition. New York: McGraw-Hill, 2000.

4)Pain Receptor Anatomy, The introductory page of a website discussing neurobiological basis for pain.

5)Brain Briefings, An excerpt from the Society of Neuroscience web page discussing nociceptors and pain.

6)Nociceptors, A paper describing the molecular identity and function of nociceptors.

7) Pain: Past, Present, and Future. , An article published by Ronald Melzack.

8)Pain, A general website discussing the causes and treatments of pain.

9)MEG Research on Pain, A research piece discussing MEG and pain.

Comments made prior to 2007

The discussion, The Percept of Pain, is remarkably insightful. While I have practiced neurology for 25 years and work with academic researchers in the pain field, this article is as sophisticated in its conceptual frameworks as any I come across from people within the field of pain.

I particularly found the discussion of Melzack's notion about neural frameworks for experience unfounded in actual experience to be insightful. This is, of course, not the common framework used in the analysis of behavior development (which, rather, presumes that behavior develops as a response). However, I think the formulation is correct--at least for some sub-systems. Notable in this regard are "genetic behaviors"--behaviors wired into the system which are not learned but rather become active in life based on experiential or temporal triggers. Among these are a human baby's first cry and a wildebeest foal's mandate to walk immediately. However, there are also more complex example such as the Monarch butterfly's migration which spans three generations in a single circuit: obligating that "experiential knowledge" has to be pre-wired into the butterfly's genome.

While we don't generally think about it, I suspect that a large portion of the geonome is devoted to phylogenetically learned behavioral programs: that is, not what we should look like but what we should do. The phantom limb information mentioned by the author is related to this: providing an organization for response to what is genetically-anticipated experience.

Interesting. (And, by the way, this throws a new light on "the mind".) Thanks ... John Barbuto, 9 February 2007