Neuronal Plasticity

A characteristic feature of FMS is hyperalgesia (increased sensitivity to mechanical, thermal, and electrical stimuli) and allodynia (painful response to normally non-noxious stimuli). These are likely to be due to altered mechanisms within the CNS such as "wind-up" and central sensitiza-tion which have been demonstrated in FMS patients.49, 50 Altered pain processing has been illustrated by studies using functional magnetic resonance imaging (fMRI) where painful pressure stimuli result in increased cerebral blood flow in areas associated with activation by noxious stimuli. This is exaggerated in FMS patients at stimulus intensities that may otherwise be seen as non-noxious.51 High levels of catastrophizing were also associated with increased activity in similar areas,52 as was depression.15 (See Table 42.1.) Neither catastrophizing nor depression affects hyperalgesia, therefore other mechanisms must also be involved in fibromyalgia.52,53

One of the models proposed is a "bottom to top'' approach in which regional musculoskeletal pain (for example MFP) leads to widespread and persistent pain, generalized hypersensitivity, and consequently FMS. This is based on neural plasticity of the CNS, in which persistent input or activation of peripheral nociceptors causes a change in CNS function and eventually structural changes. Although FMS appears to be due to a central dysfunction, it is the peripheral factors that are the most debilitating for the individuals affected, and the activation of the peripheral pain receptors undoubtedly plays some role in the central sensitization observed, possibly as an instigating factor.

Repetitive activation of muscle nociceptors leads to peripheral sensitization, therefore decreasing the excitation threshold and increasing the response to low level noxious stimuli (hyperalgesia). Wind-up occurs in the spinal dorsal horn, when repetitive input from the C-fiber nociceptors increases the response of the neurones. This causes increased release of substance P and glutamate activating the N-methyl-D-aspartic acid (NMDA) receptors by removing the magnesium block. Temporal summation studies have been carried out in FMS patients with intramuscular electrical stimulation. The results showed that temporal summation was more pronounced in FMS patients compared to controls, indicating central sensitization.54 Similar results were reported for FMS and whiplash patients,55 again supporting the hypothesis that localized pain (or trauma) can develop into FMS.

An epidural injection of lignocaine relieves pain and tender points in FMS,56 which supports the involvement of peripheral nociception causing the pain. In a study population of FMS patients, 87 percent reported that they suffered from localized pain before FMS. A further study demonstrated that 25 percent of chronic back pain sufferers and 21.6 percent with neck trauma went on to develop FMS.

Research also supports central sensitization in FMS as injections of ketamine in responders with FMS reduced the pain and allodynia experienced. However, not all FMS patients responded to ketamine suggesting that FMS is heterogenous and one mechanism is not universally responsible for FMS.

An alternative theory is that the model works from "top to bottom.'' In this case chronic stress and pain catastrophizing lead to FMS in the periphery. It has been

Table 42.1 Regional cerebral blood flow following various stimuli.

Brain region

Stimuli that increase blood flow Painful or nonpainful?

Contralateral primary somatosensory cortex (S1) Contralateral secondary somatosensory cortex (S2) Anterior cingular cortex

Insula

Thalamus

Mechanical

Mechanical

Mechanical

Catastrophizing

Mechanical

Aversive stimuli

Depression

Mechanical

Painful and nonpainful Painful and nonpainful Painful

Painful

Painful observed that pain catastrophizing is higher in FMS patients than in controls and other chronic pain conditions, but this may not be the preceding factor.57 Recent research has shown that fibromyalgia patients have elevated levels of substance P in the cerebrospinal fluid (CSF),58,59 which could be due to an increased release from neurones in the periphery and/or CNS.

Descending inhibition is also altered or impaired in FMS.60 Research into the diffuse noxious inhibitory control system (DNIC) has revealed that FMS and MFP patients appear to lack this function, in which normally a noxious stimuli applied to one body site would suppress pain at another site. (See Figure 42.2.)

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