This chapter presents evidence relating to acute therapies for some common arthritic conditions. It discusses the role NSAIDs, acetaminophen (paracetamol), steroids, colchicines, local anesthetics, opioids, and corticotrophin in arthritis. The major arthritides covered are crystal-mediated arthropathy, osteoarthritis (OA), and rheumatoid arthritis (RA). For gouty arthritis, most commentators favor NSAIDs as first-line therapy, but other treatment options (colchicine, corticosteroids, corticotropin [adrenocorticotropic hormone]) are also used. Corticosteroids are generally rated as a second-line therapy for crystal-related arthritis. Most expert reviews and meta-analyses find an unfavorable risk-to-benefit ratio, although some commentators do report occasional utility of the opioids for OA. For patients with OA in the acute care setting, acetaminophen remains a reasonable initial analgesic choice in selected patients. RA and juvenile RA (JRA) are treated with an array of disease-modifying agents that have secondary effects of relieving pain. Systemic or injected glucocorticoids are useful in RA and JRA.

Opioids are the benchmark against which other biliary tract analgesics are assessed. Historically, the distinction between opioids used for biliary tract pain (BTP) has been based upon differential effects on Oddi's sphincter. NSAIDs provide good analgesic effect, lack untoward effects on biliary tract pressure, and (perhaps through anti-inflammatory activity) seem to reduce the rate of progression from uncomplicated biliary colic to acute cholecystitis. Drugs acting at the cholecystokinin receptor may also be useful in acute treatment of BTP. Spasmolytic and anticholinergic drugs have been investigated as treatment for biliary colic. Calcium channel blockers are known to relax biliary tract smooth muscle. For BTP, the most potent agent in this class appears to be nifedipine.There is currently insufficient evidence to support use of nifedipine for acute treatment of BTP, and its outpatient efficacy is hindered by suboptimal pain relief and frequent headache.

Marine envenomation can result from discharging nematocysts (e.g. jellyfish, fire coral), puncturing spines (e.g. sea urchins, stingrays), or actual bites (e.g. blue octopus, sea snakes). This chapter addresses jellyfish envenomation. The emphasis is on pharmacotherapy. Antivenoms (or antivenins) may be an option for some species of sea snakes, jellyfish, stonefish, and antivenoms are known to have rapid and profound effects upon pain. For jellyfish stings worldwide, the most useful topical agent appears to be acetic acid topically applied in the 4-5% concentration found in vinegar. Acetic acid controls pain by deactivating nematocysts, thus limiting continued envenomation from attached stinging cells. The proteolytic enzyme papain has historically been reported to relieve jellyfish sting pain. Hot water immersion and opioids are also recommended for pedicellarial stings from sea urchins. There are no data on use of NSAIDs for marine envenomation.

Treating the pain of land-based envenomations is an acute care priority, since the discomfort may be both severe and long lasting. In some cases, administration of antivenom (or antivenin) can dramatically relieve pain and other symptoms of envenomation, even after failure of other approaches such as opioids and muscle relaxants. While neurotoxic envenomation should prompt close respiratory monitoring, opioids should be administered if clinically indicated for pain relief. The histamine pathway's contributions to terrestrial envenomation symptoms create a role for antihistamines (e.g. diphenhydramine) in treating land-based bites and stings. NSAIDs have been reported useful in small case series of bites from spiders such as brown recluses and tarantulas. Preliminary evidence from animal models and case reports suggests a role for NSAIDs for scorpion envenomation. Case studies suggest that corticosteroids are occasionally useful for some centipede bites, especially in cases in which Wells' syndrome (eosinophilic cellulitis) develops.

Pain of the breast is commonly classified as cyclic or noncyclic, depending on its temporal association with menstruation. Visits to ED typically involve acute, non-cyclic breast pain, with the most common etiologies being blunt trauma or infection. Ketorolac is useful for acute mastalgia and extramammary pain, especially in instances of breast pain complicated by blunt thoracic trauma. Lactation pain, caused by a combination of breast overfilling, nipple cracking, and ulceration is treated with breast pumping and occasional anti-microbials. The unclear etiology of cyclic breast pain (i.e. usually presenting during luteal phase and resolving with onset of menses) translates into lack of consensus on treatment of this form of mastalgia. The current focus of therapy is based on use of systemic or topical NSAIDs. Selective estrogen receptor modulators such as tamoxifen and afimoxifene may have a role in chronic therapy of mastalgia.

This chapter focuses primarily on thermal burns, but presents some brief points about related injuries. While the burn causes intense pain, thermal injury causes significant local and systemic responses that may both potentiate the pain from additional stimuli and alter the physiologic response to medication. This chapter focuses on pharmacologic approaches to analgesia. A survey of North American burn centers found that IV morphine is the most frequently used analgesic for wound care. While minor burn pain may be managed with acetaminophen or NSAIDs, opioids are the mainstay of therapy for moderate-to-severe burn-associated pain. Anxiolytics, particularly benzodiazepines, are useful adjuncts to pain therapy in burns. Lorazepam and midazolam are widely used for burn patients. A small pilot study of 10 patients suggested that the analgesic qualities of oral controlled-release morphine were comparable to those of continuous IV morphine sulfate infusions.

There are few rigorously conducted clinical trials assessing specific therapy for non-septic bursitis. First-line treatments of non-septic bursitis include NSAIDs, aspiration, and injection therapy with corticosteroids and local anesthetics. Patients receiving oxaprozin showed improved overall function scores on a variety of measures. Results for periarticular inflammation other than bursitis are similar to the findings for bursitis. For patients with shoulder bursitis, oral corticosteroids provide early improvement over placebo, but treatment benefit is lost after the first few weeks of therapy. Many corticosteroids have demonstrated effectiveness for injection of subacromial inflammation. For trochanteric bursitis, studies investigating intrabursal injection of corticosteroids have found efficacy similar to that reported for other bursal injection sites. One long-recognized medication-related etiology of subacromial inflammation is the use of protease inhibitors: indinavir and lamivudine. Given the obvious risks in altering these medication regimens, the ED provider should reduce dosages only after consultation with patients' physicians.

Cancer and tumor pain (CTP) is traditionally described as resulting from somatic, visceral, or neuropathic origins. NSAIDs have been deemed the preferred class for bony (or somatic) pain. Opioids have been considered beneficial for visceral, but not bony or neuropathic CTP. While agents such as sedatives may be helpful in patient management, the adjuvant medications are believed to augment efficacy of coadministered opioids or NSAIDs. Anticonvulsants are frequently used as an adjunct for the treatment of neuropathic CTP. For bone pain, bisphosphonates, in particular pamidronate and zoledronic acid, are shown in multiple trials to be effective in reducing bony CTP from metastatic disease. The corticosteroids are, at best, marginally effective as an opioid-sparing adjunct for CTP in general, this class may have a role in tumor-related bowel obstruction. The antisecretory agents aim to relieve bowel obstruction CTP and eliminate the need for uncomfortable nasogastric tubes.

The extensive use of short-term oxygen therapy in acute coronary syndrome (ACS), with rarely reported adverse effects and frequent cases of anecdotal benefit, supports oxygen administration as benign intervention for cardiac patients with pain and subnormal peripheral pulse oximetry. The pain of ACS is effectively decreased by beta-blockers. Though their exact analgesia mechanism is not known, there are several possible routes by which beta-blockers could reduce pain. Nitrates dilate the epicardial coronary arteries, their collaterals, and peripheral vessels, thus improving coronary perfusion and potentiating a favorable ratio of subendocardial-to-epicardial flow. Opioids have long been a part of the ACS treatment armamentarium. Due to its properties as a pulmonary venodilator and anxiolytic, morphine has been the analgesic of choice for ACS pain. Intravenous benzodiazepines should be used for patients with cocaine-associated cardiac chest pain. In this population, the risk of vasospasm from beta-blockers is such that these agents should be avoided.

Thoracic trauma constitutes 10-15% of all injuries, with rib fractures (RF) being common and painful. The intrathecal injection of morphine has been studied for patients with multiple RFs. If conditions are suitable for their use, the local anesthetics are the most efficacious mechanism for managing RF pain. Local anesthetics (sometimes co-administered with opioids) have also been used by the epidural administration route. This approach is associated with decreased pulmonary morbidity and mortality in patients older than 60 years of age with RF. For the majority of patients with RF, the controversy surrounding NSAIDs and delayed bone fracture healing is relevant. Used in patients with chest wall trauma, epidural analgesia produces pain relief that is superior to that produced by systemic opioids or other local anesthetic approaches. Local anesthetic administration via thoracic paravertebral block entails injecting an agent such as bupivacaine alongside the thoracic vertebrae.

This chapter focuses on pharmacological approaches to chronic low-back pain (CLBP). In CLBP, one of the major issues for the ED caregiver is use of opioids. The utility of opioids in CLBP is limited not only by their marginal analgesic efficacy, but also by the risk of addictive behavior. Although studies of truly CLBP are lacking, it is reasonable to use NSAIDs provided that potential side effects risks are incorporated into therapeutic decision-making. Some authors recommend avoiding the potential cardiovascular risk with COX-2 selective NSAIDs by instead prescribing dual therapy with a non-selective NSAID and a proton pump inhibitor. A 2003 meta-analysis found five RCTs demonstrating some CLBP relief with cyclic anti-depressants. The benefits of these cyclic anti-depressants are independent of their anti-depressant effects, since studies demonstrating the agents' efficacy excluded patients with clinical depression.

Serotonin 5-HT1B/D agonists, collectively known as the triptans, are a firstline abortive treatment for cluster headache (CH). Long experience supports use of inhaled oxygen therapy for treatment of debilitating cluster attacks. The anecdotal evidence is complemented by a non-placebo controlled trial showing that inhaled oxygen is effective in CH. The somatostatin analog octreotide has been shown to inhibit vasopeptides released during CH episodes. Numerous ergot alkaloids have been used for treatment of CH. The only agent that has been recently studied is the inhaled form of the ergot derivative dihydroergotamine. Results from an uncontrolled, open-label study suggest a potential role for the atypical antipsychotic olanzapine in CH. NSAIDs are useful in some rare headache types that are similar to CH, but the current balance of evidence argues against utility of indomethacin or other NSAIDs in true CH. The use of opioids for CH is anecdotally reported for CH and variants.

Based upon their widespread effective use and reported results from meta-analysis of five RCTs, topical NSAIDs are the analgesic treatment of choice for traumatic corneal abrasions (CAs). There are no studies on the use of oral or parenteral NSAIDs in CA. Opioids have not been directly assessed as analgesics for CA. Oxycodone with acetaminophen (paracetamol) is useful as a rescue analgesic in patients failing topical NSAIDs. The ophthalmology literature makes frequent reference to the analgesic utility of bandage contact lenses in CA. However, this approach is not recommended for ED use since NSAIDs work well and the contact lens approach is associated with potential infectious complications, and limited study of cycloplegic use in CA is available. There has been limited study of cycloplegic use in CA. An RCT showed no benefit as assessed by either pain score improvement or need for rescue oral analgesics.

This chapter focuses on pain in the bladder, urethra, and prostate. Interstitial cystitis is treated with heparinoids (e.g. pentosan polysulfate), botulinum toxin, or intravesical Bacillus Calmette-Guerin. There is some evidence for NSAID utility in prostatitis, but treatment for chronic prostatitis and male chronic inflammatory pelvic pain syndrome entails long-term therapy with drugs such as alpha-blockers and immuno-modulators. Antibiotics form the mainstay of urethritis treatment, with pain relief expected within seven days of instituting treatment. The best-known urinary tract anesthetic for acute care use is phenazopyridine. Ibuprofen does not reduce the dysuria or rectal pain associated with radiation therapy for prostatic cancer. However, there is some evidence for occasional NSAID utility in relieving non-infectious chronic prostatitis during the absence of other evidence for NSAIDs or other analgesics, patients with refractory pain from infectious cystitis, urethritis, or prostatitis may require opioids for relief.

This chapter addresses relief of abdominal cramping and related symptoms (e.g. pelvic pain, backache) associated with the menstrual cycle. It focuses on analgesic control of dysmenorrhea symptoms, rather than hormonal regulation of the ovulatory cycle. Prostaglandin inhibition by NSAIDs is responsible for their decades of successful use as the mainstay of dysmenorrhea treatment. An RCT in patients undergoing fractional curettage demonstrated the potent analgesic effects of NSAIDs on uterine pain. Due to the need for chronic use, the COX-2 selective NSAIDs are sometimes recommended as a treatment for dysmenorrhea. Data show that valdecoxib, administered in a single dose of 40 mg PO, provides dysmenorrhea pain relief within 30 minutes that lasts for up to 24 hours. The novel analgesic flupirtine is suggested by some to have utility in dysmenorrhea, but this centrally acting agent is not recommended owing to limited evidence and frequent side effects.

NSAIDs are widely considered as the first-line therapy for the pain associated with endometriosis. Combined oral contraceptive pills (COCPs) are generally recommended as the second-line therapy for endometriosis pain. A 2007 Cochrane review concluded that COCPs are at least as effective as gonadotropin-releasing hormone (GnRH) agonists. Medroxyprogesterone acetate is comparable to the androgen danazol, with both agents reducing pain scores by 50-74% compared with placebo. An SC form of depot medroxyprogesterone appears to relieve endometriosis as effectively as the proven approach of the GnRH agonist leuprolide acetate. Cochrane review has shown that there is generally equivalent pain relief achieved with multiple endocrine therapies for endometriosis. The myriad menopausal, androgenic, and hepatic side effects from some of the endocrine agents (e.g. danazol) used to treat endometriosis should serve to underline the importance of ED physician communication and follow-up arrangements with longitudinal care providers.

Proton pump inhibitors (PPIs) are recommended as a first-line therapy when chest pain is thought to be caused by esophageal spasm. Both long- and short-acting nitrates have been shown to provide some relief of pain caused by esophageal spasm. Calcium channel blockers decrease the amplitude and duration of esophageal spasms, but their use does not consistently result in better analgesia than achieved with placebo. This chapter discusses the use of anticholinergic agents such as atropine, hyoscyamine, or propantheline bromide decrease peristaltic contractions and reduce esophageal sphincter tone. There is evidence supporting the use of antidepressants such as tricyclics, trazodone, and SSRIs for treating chest pain caused by esophageal spasm. Regardless of their possible utility in the long term, antidepressants are not likely to be of help in the acute management of esophageal spasm pain in the ED.

Fibromyalgia is marked by high interpatient variability in both clinical course and efficacy of particular therapies. Fibromyalgia pain does not result from peripheral nociceptor stimulation but instead arises from deficient CNS processing and modulation of pain signals. Tricyclic antidepressants (TCAs) and related drugs have some efficacy when compared with placebo in clinical trials. In addition to TCAs and antidepressants, the other commonly seen approach to treating fibromyalgia pain is the use of anticonvulsants. In fibromyalgia patients taking long-term opioids, a methodologically rigorous study shows that administration of the non-ergot dopamine agonist pramipexole significantly reduces pain and improves myriad quality-of-life indices. The benzodiazepines are also associated with mixed results in fibromyalgia trials. Given the lack of inflammatory pathophysiology in fibromyalgia, it is not surprising that no data support use of corticosteroids or NSAIDs in treating fibromyalgia pain.

This chapter groups the clinically distinct, but similarly treated, entities of gastritis and peptic ulcer disease (GPUD). It focuses on patients with organic disease, with some concluding notes on the challenging management of functional dyspepsia. The most basic treatment for patients with GPUD is administration of antacids. A typical trial finds that administration of colloidal bismuth subcitrate provides significant pain relief in just over half of patients with either gastritis or duodenitis. The reason that agents such as antacids and bismuth salts are reserved for occasional symptomatic relief is that more consistent success is achieved with newer agents such as the proton pump inhibitors (PPIs). The PPIs also relieve symptoms better than does the gastroprotective agent sucralfate when altered gastroduodenal motility is a postulated occasional cause of gastritis, the prokinetic drugs have been employed to treat GPUD.

Opioids such as morphine are often used early in patients subsequently diagnosed with gastroesophageal reflux disease (GERD). Antacids provide GERD relief by buffering the refluxed gastric contents. Antacids are readily available, relatively safe, and fast acting. Antacids constitute first-line GERD therapy in pregnancy. Proton pump inhibitors (PPIs) are a first-line treatment for non-cardiac chest pain, and for GERD in particular. H2-receptor antagonists such as ranitidine (150 mg PO as needed for GERD pain) have been shown in double-blinded trials to achieve better on-demand pain relief than antacids. Prokinetic drugs such as metoclopramide and cisapride are postulated to relieve GERD by increasing resting lower esophageal sphincter tone and increasing gastric emptying. The novel prokinetic agent itopride has promising preliminary results in an open-label GERD trial, but recommendation for its acute care use must await further data.

This chapter addresses perianal painful conditions encountered in the ED setting. Laxatives are the initial therapy for perianal pain from a variety of conditions. Topically applied nitroglycerin is widely recommended for pain caused by either anal fissures or thrombosed external hemorrhoids. The utility of NSAIDs in post-hemorrhoidectomy pain is demonstrated by trials of perioperative administration of agents such as ketorolac and diflunisal. For patients with chronic anal fissure or painful external hemorrhoids who fail nitroglycerin therapy, or who have intolerable side effects to the drug, calcium channel blockers have been recommended as an alternative means to reduce anal tone and relieve symptoms. Perianal pain may also be the presenting complaint for patients with Condylomata acuminatum.The systemic condition lichen sclerosus, usually treated with potent topical corticosteroids, causes perianal (and vulvar) pain that can be significantly alleviated with topical 1% pimecrolimus cream.

The ED physician frequently encounters patients with migraine headache (MH). The ergot alkaloids, available in myriad formulations, are among the oldest drugs used for MH. Clinicians noted that MH pain was often alleviated before the real analgesic was administered by prompting interest in the use of antiemetics as stand-alone therapy. Like the antiemetics, the triptans are useful in myriad benign headache syndromes. Clinical trial evidence from the ED demonstrates sumatriptan's equal efficacy in migraine, probable migraine, and tension-type headaches. Controlled trials demonstrate efficacy of multiple NSAIDs for MH pain. Among those drugs performing better than placebo are aspirin, ibuprofen, tolfenamic acid, diclofenac, and naproxen. Despite their non-specific mechanism of action, opioids are frequently used for MH. Prophylactic medications that may have ED utility in the earliest stages of migraine include the beta-blockers (e.g. metoprolol, propranolol) and the calcium channel blockers.

Available evidence for treating pain caused by mucositis (inflammation of the digestive tract's lining) and stomatitis (mucositis involving the mouth) can be categorized into two general categories, depending on whether or not the stomatitis is related to cancer therapy (either chemo-or radiation therapy). This chapter addresses cancer treatment-associated stomatitis (CTAM). For CTAM that does develop, pain can be severe and opioids are the therapeutic mainstay. In fact, CTAM pain often necessitates IV morphine and even hospitalization and institution of a PCA regimen. Local anesthetics such as tetracaine or lidocaine are often recommended for CTAM, but their utility is not definitively demonstrated. Most of the data dealing with non-CTAM mucositis addresses aphthous ulcer (AU) treatment. Topical sucralfate is an example of an approach that is not successful in CTAM but found useful in AU. The chapter concludes with an overview of the evidence, lesser in quality and quantity, addressing non-CTAM stomatitis.

This chapter separates mechanical strain spinal pain (MSSP) from neck and back pain of other etiologies (e.g. spondylosis, radiculopathy), as there are different therapeutic approaches. The NSAIDs are the mainstay of therapy for non-radiating mechanical back pain, and by extrapolation of evidence from back pain studies, for neck strain. Opioids are the preferred treatment for MSSP in patients who have not responded to, or who cannot take, NSAIDs. Muscle relaxants are often prescribed for sprains and strains of the neck and back. Commonly used muscle relaxants include cyclobenzaprine, orphenadrine, metaxolone, methocarbamol, carisoprodol, and chlorzoxazone. Benzodiazepines have skeletal muscle-relaxing properties, and so this class (most notably diazepam) is occasionally prescribed for MSSP. Trigger point injection with local anesthetics is occasionally effective for some patients with neck or back pain, but injection therapy for MSSP has been insufficiently studied to recommend its routine use.

The etiologic differences between radiating spine pain (RSP) and other causes of neck and back pain translate into differences in therapeutic approach. This chapter focuses on pharmacologic treatment modalities for RSP. Patients with refractory RSP often require opioid therapy, but available evidence does not support specific recommendations. Studies suggest no incremental benefit, compared with NSAIDs, for PO low-potency opioids (e.g. codeine) or agonist-antagonist agents (e.g. meptazinol, ethoheptazine). The authors believe that the main role for low-potency opioids in RSP is for use in patients who fail, or do not tolerate, other therapies such as NSAIDs. Corticosteroids have been used for the treatment of acute RSP since 1960s. The injection of corticosteroids into the epidural space is a commonly used approach. A single dose of methylprednisolone significantly reduces pain scores in RSP, but the effect is small in magnitude and limited in duration.

This chapter groups neck and back pain from spinal stenosis, as well as intervertebral disk disease, or arthritis, into the category of spinal spondylitic syndromes (SSS). NSAIDs are frequently used to treat pain from these disorders despite the scant evidence support for their use in SSS. Few data address efficacy of opioids for SSS. A trial in patients with spinal osteoarthritis showed significant pain reduction compared with placebo from either regular formulation oxycodone plus acetaminophen, or sustained-release oxycodone. There is preliminary evidence supporting some role for gabapentin in cervical SSS pain. Endorsement of gabapentin use for SSS pain is based primarily upon its presumed benefit in related pain syndromes such as diabetic neuropathy. The omega-3 fatty acids eicosapentaenoic acid and decosahexaenoic acid, which have known anti-inflammatory properties, are used for SSS pain of discogenic nature.

This chapter covers both types (1 and 2) of complex regional pain syndrome (CRPS). CRPS type 2, also known as causalgia, is a true neuropathy. Of all of the types of neuropathic pain, CRPS (either type) is the most resistant to pharmacotherapy. Even traditionally endorsed approaches such as sympathetic blockade are found poorly efficacious in Cochrane review. In fact, RCT evidence does not conclusively confirm utility for any agent for CRPS. For CRPS type 2, two trials of IV infusion of bisphosphonates find that pain may be reduced by alendronate or clodronate. The anticonvulsant gabapentin, effective in a broad range of neuropathic pain syndromes, is of little utility in CRPS. There is limited evidence for use of systemic corticosteroids for CRPS type 2. This chapter finally discusses a small trial, assessing PO prednisone that has found some benefit compared with placebo.

Treatment decisions regarding diabetic neuropathy (DN) can be made based on useful evidence. Many agents have been assessed for therapy of DN pain, and many have some role in relief of symptoms. The opioid tramadol, which has additional (monoamine-related) mechanisms of analgesia, has particular utility in DN. The tricyclic antidepressants (TCAs) are among the most consistently effective therapy for neuropathic pain. Multiple RCTs have demonstrated the efficacy of the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine in the treatment of DN. A withdrawal syndrome can occur if the SNRIs are abruptly discontinued. Anticonvulsants are a valuable therapeutic option in DN. Pregabalin is effective for DN as well. Topical application of local anesthetics may be useful in patients with focal DN pain. Patch application of lidocaine is known to be effective in DN. Intravenously injected local anesthetics have been reported potentially useful in DN.

This chapter describes the effectiveness of the following agents in treating HIV-related neuropathy (HIVNP): anticonvulsants, antidepressants, acetyl-L-carnitine, cannibis, memantine, intravenous immunoglobulin, lidocaine, thalidomide, and capsaicin. Neuropathy is common in patients infected with HIV. Unfortunately, HIV-related neuropathy (HIVNP) is resistant to many of the drugs that are generally helpful in neuropathic conditions. Cochrane review has found, for instance, that antidepressants are ineffective for treating HIVNP. Neurotoxic neuropathic pain is improved by treatment with the neurotrophic support drug acetyl-L-carnitine. An RCT assessing use of cannabis cigarettes found this approach reduced pain compared with placebo. Although intravenous immunoglobulin (IVIG) is often used for treating HIVNP, critical reviews of available data reveal insufficient evidence to support a recommendation for its acute care administration for this indication. Topical therapy with capsaicin is recommended for HIVNP by some editorialists and expert reviews.