Running head: PAIN MANAGEMENT
The Painful Truth: A Comprehensive Review of Pain and Pain Management
Cameron S. Wasson
Psychology 3227B, University of Western Ontario
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Running head: PAIN MANAGEMENT
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The Painful Truth: A Comprehensive Review of Pain and Pain Management
“The greatest evil is physical pain” (St. Augustine, n.d.). These words, spoken by
Saint Augustine, a fifth century philosopher, converge on the idea that the most
malevolent things plaguing humanity take root in the existence of physical pain. To
elaborate further, “a recent market research report indicates that more than 1.5 billion
people worldwide suffer from chronic pain” (Pleis, Ward, & Lucas, 2010). It is safe to
say that pain is an unfortunate vicissitude all humanity must face; it is universal and
inevitable. Because of the ubiquitous nature of pain, researchers and psychologists
wish to describe, explain, predict, and control the very nature of it; however, there are a
multitude of dilemmas with doing so. Firstly, pain has many ethical constraints for
human testing. Most experiments of pain are restricted to animal models, which begs
the question: How can researchers quantify data on those unable to convey what they
are feeling? Secondly, pain seems to have variation from person-to-person. Thus, it is
hard to operationalize and not easy to apply to multiple models using the same
definition of pain. Aside from the two major dilemmas, researchers are making
substantial progress in the study of pain and pain management. They are also using
inductive observation, and applying a variety of treatments to converge on a universal
pain theory. Because the theories of physiological mechanisms of pain are still relatively
new, it is not always clear why these treatments work the way they do. This literature
review hopes to provide a comprehensive understanding of pain by providing a brief
history of theories, describing the physiological circuits involved, reviewing clinical
treatments of pain, and examining neural manifestations of pain.
Theories of Pain
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Much like most psychological postulates, the first theories of pain root
themselves in ancient Greek philosophy, where prominent figures such as Aristotle,
believed pain was caused by evil spirits entering ones body and inflicting harm
(Vertosick, 2001, p. 72). At the turn of the 16th century, French philosopher René
Descartes proposed the idea that pain was due to an interaction between the body and
the soul. He hypothesized that nerves were hollow tubes, which acted like ropes, and
that when a noxious stimuli were encountered the nerves would ‘pull’ and cause the
brain to produce the perception of pain (Vertosick, 2001, p. 109). While Descartes
theory may be viewed as primitive, some of his ideas are carried onto many modern
theories.
Today there are three primary theories of pain which scientists use as the basis
of their research: the specificity theory, the peripheral pattern theory, and the gate
control theory of pain. Von Frey brought the specificity theory to light during the 19 th
century, where he hypothesized that specialized peripheral receptors in the tissue sent
impulses to the brains pain region in the brain (Helms & Barone, 2008). The peripheral
pattern theory suggests that pain is perceived in a pattern-like fashion, where different
firing patterns of nerves essentially summate and create the sensation of pain. It is
important to note that in the pattern theory supporters do not believe in specific pain
receptors, but rather a integration of various types of touch receptors that cause one to
perceive pain. The gate control theory suggests more detailed physiological interactions
than the latter two theories. Melzak and Wall (1965) suggest that painful stimuli activate
two different nerve fibers; myelinated Aδ-fibers, which are the first to respond and fire to
more discriminative pain sensations; and unmyelinated C-fibers, which respond slowly
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and transmit a more diffuse pain sensation (Dubuc, n.d.). Both Aδ-fibers and C-fibers
feed into transmission cells (T-cells), which transmit the painful stimulus to brain;
however, modulating this event of pain transmission occurs via the substantia
gelatinosa (SG), a group of cells in the dorsal horn of the spinal cord. When
experiencing a painful interaction, Aδ-fibers inhibit the SG and produce a sharp fast
pain. After this, the C-fibers slowly fire and produce the dull aching pain. The process
known as the gate control theory because the SG acts as a gateway, which the noxious
stimulus must override to cause the perception of pain. One important fiber not
mentioned is the Aβ- fiber, an A-fiber subtype that transmits non-noxious mechanical
stimuli. According to the gate control theory of pain, “if touch receptors (Aβ fibers) are
stimulated, they dominate and close the gate” (Helms & Barone, 2008). This theory
suggests that massage-type therapies can be used in the treatment of chronic pain in
patients (Adams, White, & Beckett, 2010).
Afferent Pathway of Pain
The modern theory of pain is an integrated model of the specificity theory and
gate control theory. There are three major components to the experience of pain:
transduction, transmission, and perception. Transduction begins with the introduction of
a noxious stimuli and the conversion of the stimuli into an impulse by a specific
receptor. These receptors are coined nociceptors (Sherrington, 1903). When one
becomes injured, the synthesis of arachidonic acid takes place at the site of injury,
where it is converted to prostaglandins by the cyclooxygenase enzyme (COX). This
then acts on C-fibers, which lowers the pain threshold. This is why just by lightly
touching an injured area can cause severe acute pain. From the site of injury, a
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nociceptor is activated and fires and transmits an action potential along Aδ-fibers and Cfibers, where they synapse onto the substantia gelatinosa in the dorsal horn of the
spinal column (Dubuc, n.d.). The fibers then cross over at the anterior white
commissure and ascend via the anterior spinothalamic tract. The anterior spinothalamic
tract then splits into two distinct tracts; the neospinothalamic tract, which projects fast
pain (Aδ-fibers) to the ventrobasal complex of the thalamus; and the
paleospinalthalamic tract, which joins the fast tract then terminates in the hypothalamus
and limbic structures (Mohr-Catalano, 1997). The neospinothalamic tract relays
information to the somatosensory cortex; where pain is perceived, while the
paleospinalthalamic tract projects to the periaqueductal gray (PAG), the raphe nucleus
(RN), the hypothalamus, and other limbic structures; this where emotional pain is
integrated (Kozlov et al., 2012). This afferent model of pain is sometimes referred to as
bottom-up processing since there is no central input until the latter stages of the
pathway. It is interesting to note that this model, although more detailed, parallels with
Descartes theory he proposed back in the 16th century. Simplified, this pathway is
essentially a string that connects to the brain and when a noxious stimulus is
introduced, it projects to the control center. This theory is important because it is how
most pharmaceutical companies look to target pain.
Therapeutic Models for Bottom-Up Processing
Drug companies and alternative medicines such as acupuncture attempt to target
or cut off the afferent pain fibers by intervening at different levels of the pathway. Aspirin
and other non-steroidal anti-inflammatory (NSAIDS) drugs work by inhibiting the COX
enzyme (Derry, Moore, & Rabbie, 2012). By shutting off the enzyme arachidonic acid
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never gets converted into prostaglandins therefore, the threshold of pain fibers is not
reduced and allodynia, pain to non-noxious stimuli, does not occur. Alternative
medicines like acupuncture and transcutaneous electrical nerve stimulation are believed
to cut off the ascending pathways by activating Aβ-fibers, which turn on the SG
inhibiting T-cells (Chang, 2013). This can be seen through a common reflex. As one is
injured the individual tends to pull away or either shake or rub the affected area. It is
thought that this again stimulates large Aβ-fibers and inhibits the transmission of pain.
Though this model seems to be rather comprehensive there are some flaws. For
example, the cutting of small fibers (C-fibers) seems to alleviate pain in some instances
and does not in others (Pritchard & Alloway, 1999, p. 107). As well, there seems to be
another major loophole in the modern pain theory, and that is the existence of phantom
limb pain. The amputee experiencing phantom limb pain does not have nociceptors in
the afflicted area, so how could there possibly be pain coming from that region? How
can physicians cut or block a pathway that is no longer present? This alludes to the
concept that pain is nothing more than a cognitive process and perhaps is only a
product of the brain. This idea leads to the existence of another processing pathway.
Efferent Pathway of Pain
This idea that pain is nothing more than a cognitive illusion begins with the
efferent route of pain. Of the two, the efferent pathway is the most poorly understood
and an area where much research is being done. The purpose of this pathway is to
inhibit the afferent pain information by responding to incoming nociceptor information
from the peripheral nervous system. It was found that noxious stimulation excites
neurons in the nucleus reticularis gigantocellularis (RGC), which in turn stimulates the
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PAG and the RN (Braz, Enquist, & Basbaum, 2010). Next, the PAG sends its fibers to
the RN where:
Serotonin is released from the raphe nuclei and descends to the dorsal horn
of the spinal cord where it forms excitatory connections with the "inhibitory
interneurons” the substantia gelatinosa. When activated, these interneurons
release endogenous opioid neurotransmitters, which bind to mu-opioid
receptors on the axons of incoming C and A-delta fibers carrying pain signals
from nociceptors activated in the periphery. This inhibits [action potential]
from these incoming first-order neurons and, in turn, inhibits [the pain signal].
(Basbaum & Fields, 1978)
This pathway is sometimes referred to as the top-down model of pain because of the
efferent output to the spinal cord. This top-down model also seems to have a cognitive
interaction at some conscious level, and perhaps can be controlled. This pathway is
also body’s main response to noxious stimuli, as it produces pain-reducing molecules
termed endorphins. This model of pain is held in high regards, especially in the clinical
practice. Analgesics such as morphine monopolize on this system as exogenous
endorphins to completely alleviate or remove the sensation of pain
Therapeutic Models for Top-Down Processing
The therapeutic drugs that act on this model interact with the opioid receptors
found on the axons of the incoming Aδ-fibers and C-fibers. Drugs such as morphine and
heroin reduce pain by acting on these systems. A study by Bood, Kjellgren, and
Norlander (2009) showed that floating restricted isolated stimulation to be an effective
form of pain treatment because of the release of endorphins this intervention seems to
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promote. Other pain treatments such as deep brain stimulation have been shown to be
an effective way to reduce pain in chronic cancer patients (Young & Brechner, 1986).
One of the best methodologies for studying the effectiveness for treatment is to
introduce the drug Naloxone, an opioid antagonist, which inhibits the effectiveness of
endorphins. The pain reveling effects of eletroacupuncture in rats have been shown to
reverse when Naloxone is subcutaneously introduced (Pomeranz & Chiu, 1976). This
suggests that acupuncture indeed exhibits its affects by acting on the top-down model
of pain, which is contrary to what was previously stated. Some of the most interesting
treatments administered are placebos. Because there is an emotional and cognitive
component to pain, placebos seem to play a role in pain modulation. Grevert, Albert,
and Goldstein (1983) showed that naloxone diminished the analgesic effectiveness of
the placebo. This suggests that the placebo effect actually causes the release of opioids
and endorphins.
Neuropsychological Representations of Pain
Research implies there is no specific part of the cortex responsible for the
perception of pain; it is widely distributed throughout the brain (Talbot et al., 1991).
Although pain perception seems to lack a locus, the anterior cingulate cortex (ACC)
seems to play a role in pain interpretation. Davis et al. (1997), using fMRI, showed there
is a significant correlation between pain intensity and the amount of activation.
Interestingly enough, the anterior cingulate cortex is a major player of the limbic system;
therefore, perhaps all pain really only dependent on the emotional context of it.
Sawamoto et al. (2000) conducted an experiment where they evaluated the expectation
of pain in relation to the activation of the ACC. The participants were told the stimulus
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would be warm; they showed little activity; were told it was going to hurt; they showed
substantial activity; then presented the warm stimulus and were simultaneously told it
would hurt; they again showed substantial activation. Because the participants were told
the stimulus was going to hurt they reacted in a way to the warm stimulus differently
than they initially did when they were told it was warm. This goes to show that pain is
context specific and that it can be experienced differently with individual mindsets. As
well, pain also seems to be attenuated by external cues. A study by Miron, Duncan, and
Bushnell (1999) showed attention to pain to be an important component of pain
perception. Researchers introduced a noxious-thermal stimulus to participants and
monitored cortical activation, which showed a substantial response. The participants
where then given headphones and asked to attend to the music; this almost seemed to
relocate activation to the auditory cortex and minimized the activation in “pain areas.”
These aforementioned studies suggest that pain is nothing more than an illusion
created by the brain and that it may be controlled on some conscious level.
Future Directions
More conclusive studies need to be done to truly understand pain. Researchers
use inductive reasoning for the study of pain, and this is why there are so many findings
that are unequivocal and varied. The better scientists can understand both the top-down
and bottom up models of pain the more efficient and effective the treatments will
become at targeting and alleviating chronic pain. But for now pain-specific therapies
must wait, and that is the painful truth.
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