Handbook of Psychology

180 Arthritis and Musculoskeletal Conditions

There is evidence that in RA, both the T cells and cyto-
kines are integrally involved in disease activity (for review,
Smolen et al., 1996). Compared to healthy controls, RA pa-
tients have increased Il-1 levels in sera (Symons, Wood,
DiGiovine, & Duff, 1988) and increased levels of soluble
Il-2 receptors (sIL-2R) in sera and synovial ”uid (Keystone
et al., 1988). In addition, compared to OA patients, RA
patients have higher sera and synovial levels of Il-6
(Okamoto et al., 1997). Besides evidence for elevated cy-
tokine levels in RA patients, some researchers have found a
positive relationship between sIL-2R levels and disease ac-
tivity (Harrington et al., 1993; Wood, Symons, & Duff,
1988). Furthermore, although few studies have investigated
the role of cytokine activity in FM, there is preliminary evi-
dence suggesting elevated soluble IL-6 receptor (sIL-6R) and
soluble IL-1 receptor (sIL-1R) levels in FM patients, and in
depressed patients (Maes et al., 1999).
As mentioned previously, cytokines play a feedback role
on the stress systems of the body. For example, in samples of
RA patients, there is evidence that cytokines activate the HPA
axis, stimulating release of cortisol, perhaps in an effort to
suppress in”ammation (Geenan et al., 1998; Neeck et al.,
1990). Furthermore, in a sample of FM patients, cytokine in-
fusion led to exaggerated SAM responses, which stimulate
the immune system (Torpy et al., 2000). These results suggest
that understanding the immune-endocrine relationship may
be key to understanding the physiological mechanisms that
underlie stress-related illness activity in RA and possibly FM.

The Pain System

From the previous discussion, it should be clear that although
RA, OA, and FM differ from one another they also have
many things in common. Not only are they often treated
within the same medical specialty, but they also share com-
mon symptoms. These disorders are inherently associated
with chronic pain, chronic pain, which may serve as the com-
mon denominator for each of these conditions. De“ned by
the International Association of the Study of Pain as •an un-
pleasant sensory and emotional experience associated with
actual or potential tissue damageŽ (Merskey & Bogduk,
1994), pain is best understood by considering biopsycho-
social factors within a diathesis-stress model. In this section,
we describe the gate control theory of pain, and its relevance
to RA, OA, and FM.
Although both the HPA and SAM originate in the CNS,
their target organs lie outside the CNS. However, there is
also evidence of stress-related changes within the CNS that
directly affect pain perception, or nociception, a common
symptom to all arthritis-related conditions. One model that

describes the role of the CNS in nociception is the gate con-

trol theory of pain. Developed by Melzack and Wall (1965),

the gate control theory of pain represents an attempt to con-

sider the sensory, affective, and evaluative components of

pain within an integrated neurophysiological framework. The

crux of the gate control theory of pain is that both ascending

(i.e., input to brain) and descending (i.e. output from brain)

factors affect the •openingŽ and •closingŽ of a pain gate

located in the dorsal horn of the spinal cord (Figure 8.2).

Pain promoting, or nocioceptive, signals open the gate to pain

perception at the brain level, whereas antinociceptive, or

pain inhibiting, signals close the gate to pain perception. No-

ciceptive and antinociceptive signals may originate either at

the brain or spinal cord level. Therefore, both the brain and

spinal cord act in concert to either open or close the gate.

Thus, due to its emphasis on the important roles of biological,

psychological, and social factors, the gate control theory of

pain is a biopsychosocial formulation of pain systems.

Pain signals are usually transmitted from the site of injury

to the spinal cord via A-delta and C-“bers (Melzack & Wall,

1965). A-delta “bers are characteristically small and have

myelinated axons, a feature that accelerates the rate of trans-

mission to the spinal cord. As a result, A-delta “bers tend to

Figure 8.2 Pain elicits a signal in a pain receptor, which transmits the signal

to the dorsal horn of the spinal cord. The pre-synaptic neuron releases sub-

stance P into the synpase, which excites the post-synaptic neuron. The post-

synaptic neuron then sends the painful signal to the somatosensory cortex

via two different pathways: (1) directly through the thalamus, or (2) through

the thalamus after processing by the limbic structures. In the somatosensory

cortex, the pain sensation is consciously experienced.

Postsynaptic neuron

Presynaptic neuron

Pain receptor

Dorsal horn

Limbic structures

Substance P

Somatosensory cortex