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The Hip Replacement Patient

Pain that transforms from peripheral to central pain can create treatment dilemmas for many pain practitioners. If not rapidly controlled, microglial cells may release excitatory amino acids, such as glutamate, nitric oxide, and proinflammatory cytokines, which damage central nervous system tissue.
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A similar loss of inhibitory control also may occur in the brain, which may result in pituitary overstim-
ulation and excess sympathetic discharge recognized by hypertension, tachycardia, mydriasis, diaphoresis, hyperreflexia, and vasoconstriction exhibited by cold hands and feet. Patients may exhibit elevated ESR and CRP levels, both of which are nonspecific markers of inflammation including neuroinflammation. Pituitary over-
stimulation may cause elevated adrenal and gonadal hormone serum levels including cortisol, pregnenolone, and testosterone. If the overstimulation process goes on too long, the pituitary and adrenal glands may become exhausted, at which time cortisol and other adrenal–gonadal hormones may show low serum levels. Table 2 provides a diagnostic summary chart that includes a check list to help diagnose central pain. Practitioners should attempt to classify each chronic pain patient as to whether he or she has peripheral or central pain, or a combination of both.

Can Central and Peripheral Pain Coexist?
Many patients with central pain respond somewhat to some peripheral treatments because the peripheral site has never totally healed. The fear is that peripheral pain sites will remain active and continue to foster neuroinflammation in the CNS.

A recent study of 18 patients with chronic low back pain examined whether aggressive measures (spine surgery or facet cortisol injections) for low back pain could reverse brain tissue loss. By reviewing functional MRIs, the authors found that
6 months after treatment, patients in the treatment group had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls.23

The authors noted that increased DLPFC thickness correlated with the reduction of both pain and physical disability. In summary, every effort should be made to cure active, peripheral pain to prevent or minimize CNS neuroinflammation and central pain.

The Central Sensitization Disorders
In recent years, some observers have referred to fibromyalgia (FM), irritable bowel syndrome (IBS), and interstitial cystitis as central sensitization disorders. With FM in particular, there are typical, central pain signs and symptoms including constant pain “all over,” insomnia, allodynia, hyperalgesia, pituitary–adrenal hormone abnormalities, and excess sympathetic discharge manifested by such signs as hypertension, tachycardia, and cold extremities.15,17 “Sensitization” refers to glial cell activation and neuroinflammation so that a stimulus like touch or pressure causes exacerbated excess pain (hyperalgesia). One argument about these so-called central sensitization disorders is whether the pain originated in the periphery and transformed into central pain or whether the pain arose in the brain. For example, some investigators believe that most FM pain originates around a bony structure such as the cervical spine.

Other cases, including IBS and interstitial cystitis, may originate in the CNS possibly as a result of exposure to a virus or toxin. Certainly, it is well known that central pain can originate in the CNS as neurologic conditions, including stroke, multiple sclerosis, Parkinson’s disease, and amyotropic lateral sclerosis. These conditions all have neuroinflammation, apoptosis, and reformation as an underlying mechanism.

Many pain treatment regimens now in use consist of opioids, anti-inflammatory agents, antidepressants, stimulants, and neuropathic agents and have, without realization, been more directed at central rather than peripheral pain. They should continue to be used until a better understanding of central pain emerges.

It must be clearly recognized, however, that these agents are all symptomatic, not curative. I believe that our challenge is to regenerate CNS tissue, and that will have to be at least partially done with anabolic hormones that are known to effect CNS cells. Trials are currently under way to test human chorionic gonadotropin progesterone, pregnenolone, and oxytocin.

Among the recent great discoveries in pain science is that peripheral pain may transform into central pain. This phenomenon occurs when damaged nerves emit chemical substances that activate microglial cells in the CNS. Microglial cells initially produce a neuroprotective inflammatory response, but this response may give way to a destructive neuroinflammatory reaction that damages and destroys CNS cells. As damaged cells try to reform, the memory or perception of pain is permanently imprinted or encoded in them. Brain tissue loss and atrophy can be so significant that it can be observed on an MRI.

The historical clinical hallmarks of central pain are that it is constant (ie, “24/7” in the words of patients) and the patient will report little or no response to peripheral treatments such as corticoid injections, surgery, electromagnetic measures, acupuncture, and topical anesthetics. Physical examination may reveal allodynia or hyperalgesia in the early phases of central pain, but when central pain establishes itself, the peripheral pain site will not exhibit the usual findings of swelling, redness, elevated temperature, or pain on pressure. Laboratory findings may show elevated inflammatory markers (ESR, CRP). The pituitary–adrenal–gonadal axis is overstimulated in central pain and may show abnormal cortisol, and other hormone levels. Excess sympathetic discharge is almost universal and manifested by hypertension, tachycardia, mydriasis, diaphoresis, and vasoconstriction with cold hands and feet. Practitioners are urged to immediately begin classifying their chronic pain patients as to whether their pain is central, peripheral, or both.

Last updated on: December 1, 2011