Many elderly patients suffer from neuropathic pain which is poorly responsive to opioid analgesics that act primarily at the μ opioid receptor (Table28.2) [66]. While affinity for μ, δ, and κ receptors of opioids are steric-dependent, the affinity of “l” and “d” forms are nearly equal with respect to nonopiate receptor actions such asN-methyl-D-aspartate (NMDA) antagonist and blockage of reuptake of serotonin and noradrenaline. Multiple actions of the broad-spectrum opioids seem to be synergistic with respect to analgesic action, similar to usingnarrow-spectrum opioids in combination with an NMDA receptor antagonist and a tricyclic antidepressant. As listed in Table28.3, theopioids that have dual actions both for opioid receptors and NMDA receptors will be more effective for neuropathic pain than the narrow-spectrum opioids. These are shown as broad-spectrum opioids.

While methadone is widely used in opioid addiction medicine for either slow withdrawal programs or for methadone maintenance programs, it is also widely used in treatment of neuropathic pain because of its triple effect as described above. It is however a difficult drug for primary care physicians because of the complex conversion from other opioids to methadone or vice versa. Douglas et al. present a systematic review of the complexities of methadone conversions [67].

Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a step 3 opioid first developed in the 1940s as an alternative to morphine. Levorphanol belongs to the morphinan opioid series. Levorphanol has greater potency than morphine and is a potent NMDA receptor antagonist. Levorphanol interferes with the uptake of norepinephrine (NE) and serotonin, which makes it potentially useful for neuropathic pain. Glucuronidation changes Levorphanol to Levorphanol-3-glucuronide with excretion by the kidney. Levorphanol has a long half-life and may accumulate with repeated dosing. Levorphanol can be administered orally, intravenously, and subcutaneously, and is therefore an ideal substitute for methadone. It should not be given together with Monamine Oxidase Inhibitors as it can lead to hypertensive crisis [68].

Because meperidine has a metabolite that acts in the brain of elderly patients and leads to confusion and even seizures, the only truebroad-spectrum opioid analgesics available are methadone, Levorphanol, and to some extent tramadol. Tramadol is only a weak opioid agonist and weak NMDA receptor antagonist, and is only available for oral administration, as is Tapentadol [69].

In 2004, for 67% of patients, the last place of care was an institution, with 38.4% dying in a hospital and 30.5% in a nursing home. Only 33% died at home; 49.3% of these were on home hospice care; 38.2% received no formal services; and 12.5% had home health care nursing services without hospice participation [70].

Reporting on the degree of satisfaction of bereaved family members with the care their loved ones received, hospice care at home received the highest level of overall satisfaction with 71% of respondents. Twenty-five percent of all patients with pain or dyspnea did not receive “any” or “enough” treatment. Inadequate pain management was 1.6 times more likely in a nursing home setting or with home health services and 1.2 times more likely in a hospital than with home hospice [70].

End-of-lifepain management for patients who are being managed at home presents problems of assessment and administration of medication. Patients who are still able to swallow can be managed with oral medications. Rectal suppositories, transdermal medications, and transmucosal medications are available.

Morphine is available in multiple preparations. Kadian^® and Avinza^® are marketed as 24-h, single-dose sustained-release morphine preparations. Although their uptake properties differ, they both have the property of being packaged in a capsule that can be sprinkled as pellets onto applesauce or added to slurry for administration down an NG- or G-tube, while retaining the sustained-release characteristic. MS Contin^® is an every 12-h sustained-release morphine preparation that cannot be broken open. Doing so destroys the integrity of the sustained-release capsule; the patient receives the entire dose as an immediate-release preparation. Oxy-Contin^® is a 12-h sustained-release preparation of oxycodone that also cannot be opened or it too becomes an immediate-release preparation.

There is currently one preparation of extended release hydromorphone (Exalgo^®) which is reported as a single dose 24 h preparation. Methadone is long acting but is not a sustained-release preparation. Fentanyl (Duragesic^®) and Buprenorphine (Butran^®) are the only commercially available transdermal opioids. Extended release Oxymorphone is marketed as Opana^® and Tapentadol extended-release oral tablets are known as Nycenta^®. Tramadol extended release has been available for some time as Ultram^® ER. Zohydro^® an extended release formulation of hydrocodone eliminates the limitation of dosage which is the result of combination of hydrocodone with acetaminophen products.

Fentanyl is available in a buccal absorption preparation. Transmucosal fentanyl citrate (OTFC) lozenge on a plastic handle; Actiq^®, was the first of its kind designed for rapid uptake of a powerful opioid analgesic. This has now been supplanted by an additional five such compounds (Effentora^®/Fentora^®, Abstral^®, Instanyl^®, Breakyl^®/OnsolisTM, and PecFent^®) concurrently approved in Europe and/or the US, and have documented efficacy in quickly relieving breakthrough pain episodes [71].

It is important to remember that sustained-release medications are encouraged for patients who have continuous pain. But it must also be remembered that activity will often increase the level of pain; patients must be prescribed rapid-onset, short-acting medications to be used for such breakthrough pain [72]. Because patients vary tremendously in their requirements for pain medication, particularly in the senior population in which the margin for error is smaller, it is important to titrate patients with immediate-release medication to determine how to convert to sustained-release medication.

Although sustained-release morphine is available in capsules that are recommended for every-12-h dosing and every-24-h dosing, the absorption characteristics will determine whether a particular patient experiences adverse effects such as nausea or sedation, or “end-of-dose” failure. It is sometimes necessary to lower the dose and change to every-8-h or every-12-h dosing. And it is important to distinguish between “end-of-dose” failures of sustained-release medications from breakthrough or activity based pain [73].

Rarely in acute pain situations and more often in end-of-life care, patients’ pain cannot be brought under control with opioid infusions alone. In such situations, optimum pain control with minimal side effects could be obtained with a combination solution of 1 mg/mL morphine and 1 mg/mL ketamine, with a lockout period of 8 min with an IV PCA [74]. These agents can both be given orally as well in the same ratio, e.g., 30 mg of immediate release morphine sulfate with 30 mg of ketamine every 3–4 h.

When patients are terminally ill and traditional analgesic regimens are unsuccessful at providing adequate analgesia and/or relief from suffering, the following solution can provide benefit [75]:

IV infusion should begin at 3–5 mL/h titrating to effect. Doubling the concentrations will allow reduction of the volume infused if needed. High concentrations can be used as subcutaneous infusion as long as the volume infused per hour remains less than 2 mL.

Regional anesthetic techniques can make an important contribution to end of life care by providing excellent analgesia or even anesthesia in an extremity, allowing for reduction in the amount of opioids. Supraclavicular brachial plexus blockade has been reported for treating the severe pain caused by a Pancoast tumor involving the arm of a terminal patient, allowing the patient relief of pain and increased mobility [76].

Neurolytic neuraxial blocks have been used for many years but no prospective randomized trials have been reported. Reports of effectiveness are based on small case report studies [77,78]. However, celiac plexus neurolytic blocks for pancreatic cancer pain has been reported in larger patient groups [79].

Theantiprostaglandin effect of NSAIDs can be beneficial during the acute phase of soft tissue injury. This biochemical effect may control the inflammatory response to injury and provide pain relief. The duration of an NSAID’s analgesic effect may be different from its antiinflammatory effect. The antiinflammatory effect may last longer than the analgesic effect.

Chronic inflammatory disease pain such asarthritis may warrant chronic NSAID therapy. But some authors have expressed concern that NSAIDs may actually interfere with the later stages of tissue repair and remodeling, where prostaglandins still help mediate debris cleanup. This does not seem to be true for the cyclo-oxygenase 2 inhibitors (COX-2) specific inhibitors . Therefore, dosage, timing, and potential side effects of NSAIDs should be evaluated. It is not possible to predict patient response to a particular NSAID by chemical class or pharmacokinetics [80].

Some authors report that osteoarthritis may not be solely an inflammatory disease of the joints (peripheral sensitization) but may also be a disease of central sensitization [81]. This complicates treatment of elderly patients with osteoarthritis.

It must be remembered that COX-2 specific inhibitors do not affect platelet aggregation and therefore may pose a risk for myocardial infarction if a patient is taken off aspirin therapy. For the same reason, it is safe to continue COX-2 specific inhibitors with daily low-dose aspirin. COX-2 inhibitors also have a safer profile from the standpoint of gastrointestinal irritation, but care should still be taken in patients with borderline renal function [82,83]. Baseline renal function tests should probably be obtained for elderly patients who are beginning a course of chronic coxib therapy or NSAID therapy. Drug holidays of 30–60 days every 4–6 months may also be advisable.

Tricyclic antidepressants are often used as adjuvants in treating neuropathic pain because of their inhibition of reuptake of serotonin and NE. The link between depression and pain may be both psychological and biological. The biological basis for depression has focused on dysregulation of the neurotransmitters serotonin (5-hydroxytryptamine, or 5-HT), NE, and dopamine [84].

There is fear that antidepressants will cause cardiac arrhythmias. Tricyclic antidepressants are safe for cardiac patients, except for several months after a myocardial infarction or if a conduction defect or persistent dangerous arrhythmia is already present [85].

Specificserotonin reuptake inhibitors (SSRIs) have safer cardiac profiles than tricyclic antidepressants. SSRIs are effective for depression.SSRIs do not have analgesic effects like the tricyclics because they are only serotonin reuptake inhibitors and not norepinephrine reuptake inhibitors. Both are necessary to modulate neuropathic pain. Tricyclics are more effective for pain and for sleep but may also cause sedation, cognitive changes, and dizziness. Elderly patients taking tricyclic antidepressants are at risk for falling, resulting in hip or other fractures. Again, titration and frequent reassessment are the key to successful treatment. In addition, many newer classes of antidepressants provide inhibition of reuptake of NE, serotonin, and dopamine without the associated sedation [86,87].

Gabapentin (Neurontin^®) and Pregabalin (Lyrica^®) are probably the most effective agents with the fewest side effects for the treatment of neuropathic pain [88]. Gabapentin is absorbed in the duodenum, not metabolized by the liver, not protein bound, excreted unchanged by the kidneys, and has no ceiling dose. It is nontoxic to the liver and kidney. The only significant side effects are sedation and cognitive impairment. Pregabalin is similarly relatively free of toxic effects, but both need to be reduced in the presence of renal insufficiency. Starting low and titrating to response again is the recommendation, but rapid titration upward is possible as tolerated. Oxcarbazepine (Trileptal^®), lamotrigine (Lamictal^®), and Topamax^® are also effective substitutes.

Evaluation by a psychiatrist may yield information about clinical depression resulting in emotional suffering perceived as pain versus sadness, frustration, and isolation in response to inadequately treated pain. This would be valuable information in making a choice of treating with an SSRI versus a tricyclic or other agent with serotonin, NE, and/or dopamine reuptake inhibition effects.

With any of these medications, tricyclic or other antidepressants,anticonvulsants , etc., cognitive impairment caused by the medication must frequently be accepted or tolerated in the elderly patients in order to obtain pain relief.

Acute, severe pain decreases insulin sensitivity. This would indicate that relief for acute pain is important for maintenance of normal glucose metabolism. Many elderly patients are diabetic, emphasizing the need for good pain relief [89].

As indicated earlier, upper extremity surgeries are amenable to brachial plexus anesthesia and analgesia. Brachial plexus nerve blocks have a prolonged duration of action in the elderly patients, approximately 2.5 times longer. This would lead to a slower return of pain and therefore easier titration of postoperative medications [90]. However, elderly patients are frequently at risk for falls before surgery, so greater care must be taken in discharge criteria after a regional anesthetic to make sure they can maintain balance and that the caregiver with whom they will be discharged home is capable of protecting them from falls.

As indicated earlier, more and more elderly patients are having more and more surgeries as our population ages. Many of these procedures are orthopedic procedures especially amenable to regional analgesics techniques providing faster recovery, earlier mobilization, and faster discharge from the hospital. In this age of cost consciousness and patient satisfaction as well as improved outcomes, it is incumbent upon surgeons to request and encourage the incorporation of regional analgesic techniques into the care of elderly orthopedic surgical patients. This is particularly important in light of physicians’ reluctance to prescribe opioids to patients, particularly elderly patients even though opioids can be prescribed safely [91].

Chronic lumbar pain as a result of degenerative arthritis is very common. Osteoarthritis is the most common cause of nociceptive pain in the elderly patients. Inflammatory pain does respond well to analgesics such as antiinflammatory medications and opioids. But as indicated previously some authors report that osteoarthritis may not be solely an inflammatory disease of the joints (peripheral sensitization) but may also be a disease of central sensitization [81]. This complicates treatment of elderly patients with osteoarthritis.

Cancer pain, myofascial pain syndromes, postherpetic neuralgia, diabetic polyneuropathy, radiculopathy or amyotrophy, trigeminal neuralgia, peripheral vascular disease, and central poststroke pain (CPSP) syndrome are all common in the elderly patients. Furthermore, arthritis of the knee, hip, and shoulder are all common problems in the senior population, and surgical replacement is very advanced and highly successful. Diagnosis is easy and fairly certain to be correct. But appropriate pain management is essential for outcomes leading to improved quality of life. Chronic pain after total hip arthroplasty seems to be a significant problem in at least 12.1% of patients [92]. And 13% of patients report moderate to severe pain at 1 year post total knee arthroplasty in spite of an absence of clinical or radiologic abnormalities [93].

CPSP is a neuropathic pain syndrome characterized by constant or intermittent pain in a body part occurring after stroke. It is associated with sensory abnormalities in the painful body part. The incidence of CPSP is 8% within the first year, but pain may appear up to 3 years after the stroke. Sixty-three percent of those who develop pain had onset within the first month [94]. Two-thirds of those who develop pain experience moderate to severe pain. This 8% incidence of pain with 5% expressing moderate to severe pain is similar to other neuropathicpain syndromes such as phantom limb pain [95], central pain in spinal cord injury [96], and pain in diabetic neuropathy [97].

About two-thirds of adults have low back pain at some time. Of the 65 million people in the United States with low back pain, approximately 151,000 undergo fusion of the lumbar spine each year [98]. The number of spinal fusion surgeries is increasing annually, in part, according to Deyo et al., because of widening indications, including the diagnosis of back pain made by discography [99,100]. Allegri et al. offer us a comprehensive review of the problems associated with diagnosis and treatment of low back pain [101].

Because of the high rate of unsatisfactory results with open spinal surgery and the more tenuous physical condition of elderly patients to undergo and tolerate open spinal surgery, less-invasive techniques for treating discogenic pain have been developed. One such procedure is percutaneous diskectomy using coblation technology. This is a percutaneous technique to reduce the volume of internally disrupted disk material [102]. Spinal cord stimulation and intrathecal drug delivery has also been moderately effective for control of pain in unremitting low back pain and radicular pain [103–105]. For chronic zygapophyseal joint (spinal facet joint) pain, radiofrequency neurotomy of the medial branch of the posterior spinal nerve ramus has been found to be effective in both the cervical and lumbar regions [106,107].

Although lowback pain is a fact of life for a substantial proportion of the population at all ages, the aged have a greater prevalence and experience greater impact on their quality of life than the remainder of the population. At the same time, they are underrepresented in research [108]. Treatment protocols are poorly defined in the elderly patients. History and a comprehensive evaluation are necessary for an appropriate strategy [109].

Epidural injections can be helpful for acute vertebral compression fractures, which are common in the elderly patients. Continuous epidural infusion of local anesthetic is also an option but requires hospitalization. Vertebroplasty is also an option. This involves a technique designed to consolidate pathologic vertebral bodies through the injection of orthopedic cement under fluoroscopic guidance [110–112]. This procedure has been shown to be safe in frail elderly patients and can improve quality of life [113].

Neurogenic claudication is frequently a presenting symptom of lumbar spinal stenosis. The patient complains of pain in the legs with walking which is relieved with rest. Epidural injections can sometimes be helpful in early disease. In advanced disease if surgery is not an option, spinal infusion therapy may be helpful as an alternative [114].

The wordherpes stems from the Greekherpein which means “to creep,” whereaszoster means “girdle.” The disease infects 800,000 people in the United States each year, and the incidence increases with advancing age. The etiopathogenesis of herpes begins after chicken pox, when the varicella virus becomes dormant in a spinal nerve. When reduced cell-mediated immunity occurs, AHZ reactivates. Reactivation leads to infection down the nerve to the skin with the eruption of skin lesions. The inflammation can also travel to reach the spinal cord or the trigeminal brainstem complex [115].

The first sign of shingles is intense pain or itching, even before the lesions erupt on the skin. It is only along one nerve on one side of the body. Treatment should start as soon as possible with antiviral medication, pain medication, and steroids. Steroids are safe in acute herpes zoster because it is an immunoglobulin G-mediated immune response [115]. Epidural injections usually are helpful only in the first 3 days after eruption. Subcutaneous infiltration of local anesthetic and long-acting steroid can provide relief and accelerate healing. Stellate ganglion sympathetic and superior cervical sympathetic ganglion local anesthetic blocks can be helpful for zoster of the face in the trigeminal distribution. Manabe et al. [116] demonstrated that continuous epidural infusion of local anesthetic can shorten the duration of zoster-associated pain.

Usually this disease is defined as pain that extends beyond the normal healing period of 6 weeks to 2 months. The pain takes on the characteristics of neuropathic pain with allodynia, and hyperalgesia. Moragas and Kierland [117] have reported on the frequency of persistent pain lasting less than 6 months and more than 12 months for various age groups. For patients less than 29 years old, the percentage of patients with persistent pain after “shingles” was 4% or less for less than 6 months and more than 12 months.

For the 30- to 69-year-olds, the frequency of persistent pain lasting more than 12 months ranged between 10% and 37%. But for patients over the age of 70 years the incidence of persistent pain for less than 6 months increased to almost 75% while persistent pain over 1 year was still almost 50%, and this continues to increase with increasing age. This is why aggressive treatment of acute herpes zoster is so important even though aggressive therapy will not prevent the development of postherpetic neuralgia. However, it will change the quality of the pain from the intense unsupportable pain syndrome to a more diffuse, deep aching pain that can be supported [118].