The benzodiazepines as adjuvant analgesics

There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful review of the literature reveals insufficient evidence to support the contention that the benzodiazepines have meaningful analgesic properties in most clinical circumstances. Treatment with the benzodiazepines may reduce complaints of pain, but this seems to be an indirect effect related to their psychotropic properties, such as alleviation of anxiety and, in selected cases, depression. In the absence of definitive data, clinical experience suggests a potential role for treatment with benzodiazepines for acute muscle spasm, concomitant chronic pain and anxiety, and lancinating neropathic pain, in which case clonazepam and alprazolam may be the agents of choice. They should probably not be considered as first-line choices even for the above indications, since potential benefits must be considered in the context of potential for the development of cognitive impairment, physical and psychological dependence, worsening depression, overdose, and other side effects.     

The use of benzodiazepines in the treatment of chest pain: a review of the literature

Benzodiazepines, although not listed in the American Heart Association's guidelines for the treatment of chest pain, are often used to provide symptomatic relief to patients who experience chest pain. To investigate the utility of benzodiazepines in the treatment of chest pain, the pharmacologic actions and cardiovascular effects of benzodiazepines were reviewed. In addition, a literature search regarding the use of benzodiazepines to treat patients with chest pain was conducted. The results indicated that benzodiazepines reduce anxiety, pain, and cardiovascular activation. Benzodiazepines amplify gamma-aminobutyric acid (GABA) throughout the central nervous system, and act more peripherally to reduce catecholamines. In addition, preliminary evidence indicates that benzodiazepines may cause coronary vasodilatation, prevent dysrhythmias, and block platelet aggregation, though further study is needed. Both non-cardiac chest pain (associated with musculoskeletal, esophageal, neurologic, and psychiatric conditions) and cardiac chest pain (associated with acute and chronic myocardial ischemia) seem to be effectively treated with benzodiazepines. Benzodiazepines are safe and well tolerated when administered alone or in combination with other medications. Moreover, the risk of dependence is minimal when benzodiazepines are prescribed on a short-term basis. Further study of benzodiazepines in the treatment of acute chest pain is needed to confirm these favorable actions and better define their use in the acute medical setting.     

Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso‐Occlusive Episodes in Adolescents with Sickle‐Cell Disease

Patients with sickle‐cell disease (SCD) can experience recurrent vaso‐occlusive episodes (VOEs), which are associated with severe pain. While opioids are the mainstay of analgesic therapy, in some patients with SCD, increasing opioid use is associated with continued and increasing pain. Dexmedetomidine, an α₂‐adrenoreceptor agonist with sedative and analgesic properties, has been increasingly used in the perioperative and intensive care settings and has been shown to reduce opioid requirement and to facilitate opioid weaning. Therefore, there might be a role for dexmedetomidine in pain management during VOEs in patients with SCD. Here, we present the hospital course of 3 patients who during the course of VOEs had severe pain unresponsive to opioids and ketamine and were treated with dexmedetomidine. Dexmedetomidine infusions that lasted for 3 to 6 days were associated with marked reduction in daily oral morphine‐equivalent intake and decreases in pain scores (numeric rating scale). There were no hemodynamic changes that required treatment with vasoactive or anticholinergic agents. These preliminary findings of possible beneficial effects of dexmedetomidine in decreasing opioid requirements support the hypothesis that dexmedetomidine may have a role as a possible analgesic adjuvant to mitigate VOE‐associated pain in patients with SCD.     

Influence of Abuse History on Concurrent Benzodiazepine and Opioid Use in Chronic Pain Patients

An important predictor of opioid overdose is co-use of benzodiazepines, which are often prescribed for anxiety. Coping with anxiety may be particularly difficult among individuals with a history of abuse, as it is often linked to higher pain severity and poorer coping skills. We explored whether abuse history moderated the association between anxiety and benzodiazepine use among current opioid users. New patients at a tertiary care, outpatient pain clinic completed self-report measures of medication use, anxiety, and physical and sexual abuse history (child abuse only, adult abuse only, or cumulative abuse). The present study included adult patients reporting current opioid use (n?=?1,785). Approximately 16% reported co-use of benzodiazepines, and 17% reported a history of abuse. Patients reporting child abuse only and cumulative abuse reported co-use of benzodiazepines and opioids more often than those denying abuse and patients reporting adult abuse only (P < .001). Multivariate logistic regression analyses showed that the probability of benzodiazepine use among patients reporting cumulative abuse increased sharply at high levels of anxiety (P?=?.003). Cumulative abuse may increase sensitivity to psychological distress and put patients at risk for co-use. Providers should be aware of life history factors, including abuse, that may drive the need for medication.Perspective: This article examines the association between history of abuse victimization and co-use of benzodiazepines among chronic pain patients reporting current opioid use. The findings suggest that cumulative victimization across the lifespan may contribute to co-use by increasing sensitivity to psychological or physical distress or by negatively impacting coping skills.     

Cancer pain management in children

Unrelieved pain may have a major impact on the care of children with cancer. The type and severity of pain experienced by children with cancer varies from acute, procedure-related pain to progressive chronic pain associated with the progression of the disease or sequelae of treatment. Drugs are the mainstay of treatment. Regular pain assessments combined with appropriate analgesic administration at regular dosing intervals, adjunctive drug therapy for control of adverse effects and associated symptoms, and nonpharmacological interventions are recommended. Although standard dosing of opioids adequately treats most cancer pain in children, more complex treatment is required by a significant group. Strategies to improve analgesia include the use of epidural or intrathecal infusions of a combination of opioids and other adjuvants, or other regional anaesthesia techniques. Procedure- and treatment-related pain is an even greater problem than cancer pain. Recommendations have been published with regard to the monitoring and personnel required when children are sedated which aim to set the standard of care and minimize both physical discomfort or pain and negative psychological responses, by providing analgesia; and to maximize the potential for amnesia; and to control behaviour.     

Clinical Uses of Intrathecal Therapy and Its Placement in the Pain Care Algorithm

Intrathecal drug delivery is an effective treatment option for patients with severe chronic pain who have not obtained adequate analgesia from more conservative therapies (eg, physical therapy, systemic opioids, nonsteroidal anti‐inflammatory drugs, antidepressants, and anticonvulsants). This review focuses on, but is not limited to, the 2 agents currently approved by the U.S. Food and Drug Administration for intrathecal analgesia: preservative‐free morphine and ziconotide (a nonopioid, selective N‐type calcium channel blocker). We describe the appropriate use of intrathecal therapy in the management of severe chronic pain, based on current best practices. Topics addressed here include patient selection, trialing, dosing and titration, adverse event profiles, long‐term management, intrathecal therapy for cancer‐related pain, and the placement of intrathecal therapy in the pain care algorithm. In appropriately selected patients with chronic pain, intrathecal therapy can provide substantial pain relief with improved functioning and quality of life. Successful long‐term management requires ongoing patient monitoring for changes in efficacy and the occurrence of adverse events, with subsequent changes in intrathecal dosing and titration, the addition of adjuvant intrathecal agents, and the use of concomitant oral medications to address side effects, as needed. Based on an infrequent but clinically concerning risk of overdose, granuloma, and other opioid‐induced complications, nonopioid therapy with ziconotide may be preferred as a first‐line intrathecal therapy in patients without a history of psychosis or allergy.     

Analgesic and sedative pharmacology in the intensive care unit

Sedation and analgesia are central elements in the care of critically ill, mechanically-ventilated patients. The goal of analgesic therapy is to provide relief from pain and physical discomfort which may lead to poor sleep, agitation, or a stress response. Opioids, such as morphine, fentanyl, and hydromorphone, are considered first-line agents for treating pain. All of these agents are equally effective at equipotent doses and the choice of an agent depends on both drug and patient characteristics. Sedatives with amnestic properties are desirable to prevent or relieve anxiety and agitation. The benzodiazepines and propofol are the primary sedative agents used in the intensive care unit (ICU). Agents such as clonidine and haloperidol may have a role in the ICU when used concomitantly with sedatives and analgesics. An understanding of the pharmacotherapy of sedation and analgesia in the ICU will help support appropriate usage of these agents and improve patient care.     

Physical agents used in the management of chronic pain by physical therapists

Evidence supporting the use of specific physical agents in the management of chronic pain conditions is not definitive; it is largely incomplete and sometimes contradictory. However, the use of agents in chronic pain management programs is common. Within the broad use of physical agents, they are rarely the sole modality of treatment. A 1995 American Physical Therapy Association position statement asserts that "Without documentation which justifies the necessity of the exclusive use of physical agents/modalities, the use of physical agents/modalities, in the absence of other skilled therapeutic or educational intervention, should not be considered physical therapy". Physical agents may serve as useful adjunctive modalities of pain relief or to enhance the effectiveness of other elements in therapy geared toward resolution of movement impairments and restoration of physical function. Given that a conclusive aggregate of findings is unlikely to exist for all permutations of patient conditions, combined with interacting therapeutic modalities, an evidence-based approach to pain management is not always possible or beneficial to the patient. In the face of inconclusive evidence, a theory-based approach may help determine if the therapeutic effect ofa given physical agent has the possibility of being a useful clinical tool in the context of treating a particular patient's mechanism of pain generation. Until controlled efficacy findings are definitive, careful individual patient response monitoring of thoughtful theoretical application of adjunctive physical agents may be a prudent approach to the management of chronic pain.     

“He Says, She Says”: A Comparison of Fathers’ and Mothers’ Verbal Behavior During Child Cold Pressor Pain

Mothers’ behavior has a powerful impact on child pain. Maternal attending talk (talk focused on child pain) is associated with increased child pain whereas maternal non-attending talk (talk not focused on child pain) is associated with decreased child pain. The present study compared mothers’ and fathers’ verbal behavior during child pain. Forty healthy 8- to 12-year-old children completed the cold pressor task (CPT)—once with their mothers present and once with their fathers present in a counterbalanced order. Parent verbalizations were coded as Attending Talk or Non-Attending Talk. Results indicated that child symptom complaints were positively correlated with parent Attending Talk and negatively correlated with parent Non-Attending Talk. Furthermore, child pain tolerance was negatively correlated with parent Attending Talk and positively correlated with parent Non-Attending Talk. Mothers and fathers did not use different proportions of Attending or Non-Attending Talk. Exploratory analyses of parent verbalization subcodes indicated that mothers used more nonsymptom-focused verbalizations whereas fathers used more criticism (a low-frequency occurence). The findings indicate that for both mothers and fathers, verbal attention is associated with higher child pain and verbal non-attention is associated with lower child pain. The results also suggest that mothers’ and fathers’ verbal behavior during child pain generally does not differ.

Perspective

To date, studies of the effects of parental behavior on child pain have focused almost exclusively on mothers. The present study compared mothers’ and fathers’ verbal behavior during child pain. The results can be used to inform clinical recommendations for mothers and fathers to help their children cope with pain.     

Noncardiac Chest Pain: A Focus on Psychogenic Causes

Patients presenting with noncardiac chest pain of psychogenic origin are one of the more challenging clinical dilemmas to primary care medicine. Key aspects to recognition of these patients are predominance of autonomic complaints, multiple presentations, clustering of physical complaints and a repeated history of negative cardiac pathology, a clinical profile of anxiety or panic disorder. Therapy can be achieved by the use of benzodiazepines. Psychiatric consultation is to be sought following successful symptom abatement from a parenteral benzodiazepine challenge in the emergency department on successive occasions.     

Opioid treatment of chronic pain in patients with addiction

Patients with a history of drug or alcohol addiction may present to physicians with pain complaints. The medical literature is weak on the treatment of pain with opioids in patients in recovery or active addiction. This is because inconsistent criteria were used to define addiction and the types of chronic pain. There are clear differences between physical dependence, tolerance, and addiction. Addiction is different from pseudoaddiction and must be determined by the patient's behavior after appropriate pain management. Long-acting opioids are often the medications of choice for moderate to severe pain control. Short-acting opioids can be used for breakthrough pain. There are many other medications that can enhance pain control as adjunctive analgesics. Drug-seeking behavior may be seen with either active addiction or pseudoaddiction, or as part of deviant behavior such as drug diversion. A way to distinguish between these conditions is by giving the patient appropriate pain medication and observing the pattern of behavior to determine which is causing the drug-seeking behavior. Safe prescribing of medications with abuse potential includes use of a medication agreement, setting goals with the patient, giving appropriate amounts of pain medication, monitoring with pill counts and drug screens, and careful documentation. Even patients with a history of addiction can benefit from opioid pain medications if monitored appropriately.     

Central Pain

ABSTRACT

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.     

Dialogues on complex analgesic strategies for difficult pain syndromes

Although the use of oral analgesics for the control of cancer pain has been demonstrated to be successful in most patients, some patients will fail to respond to pharmacological therapy or will suffer unacceptable adverse effects. Experience is accumulating that when adverse effects prevail with oral opioid administration, the analgesic response may be improved by changing the drug and/or the route of administration. Switching to an alternative opioid may further improve the balance between analgesia and adverse effects Despite optimal systemic opioid treatment, in some complicated circumstances it is necessary to find different solutions, including the neuraxial administration of multiple drugs with different characteristics, which are difficult to manage. Three case reports illustrate how complex could be the analgesic approach using multiple analgesic regimens and different routes of administration to effectively manage complex pain syndromes commonly defined as unresponsive.     

Pharmacology of oral combination analgesics: rational therapy for pain

No single analgesic agent is perfect and no single analgesic can treat all types of pain. Yet each agent has distinct advantages and disadvantages compared to the others. Hence, clinical outcomes might be improved under certain conditions with the use of a combination of analgesics, rather than reliance on a single agent. A combination is most effective when the individual agents act through different analgesic mechanisms and act synergistically. By activating multiple pain-inhibitory pathways, combination analgesics can provide more effective pain relief for a broader spectrum of pain, and might also reduce adverse drug reactions. This overview highlights the therapeutic potential of combining analgesic medications with different mechanisms of action, particularly a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen with an opioid or tramadol.     

Nebulized Ketamine Used for Pain Management of Orthopedic Trauma

BackgroundKetamine is a noncompetitive N-methyl-D-aspartate/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization and hyperalgesia. When administered via i.v. (push-dose, short infusion, or continuous infusion) or intranasal routes, ketamine has shown to be effective in patients with acute traumatic pain. However, when i.v. access is not attainable or readily available, the inhalation route of ketamine administration via breath-actuated nebulizer (BAN) provides a noninvasive and titratable method of analgesic delivery. The use of nebulized ketamine has been studied in areas of postoperative management of sore throat and acute traumatic musculoskeletal and abdominal pain. To our knowledge, this is the first case series describing the use of nebulized ketamine for analgesia and orthopedic reduction.Case SeriesWe describe 4 patients who presented to the emergency department with acute traumatic painful conditions (one patellar dislocation, one shoulder dislocation, and two forearm fractures) and received nebulized ketamine for management of their pain.Why Should an Emergency Physician Be Aware of This?Administration of nebulized ketamine via BAN can be used as analgesic control for musculoskeletal trauma, as it can be administrated to patients with difficult i.v. access, has a rapid onset of analgesic effects with minimal side effects, and remains opioid-sparing.     

Eight principles for safer opioid prescribing and cautions with benzodiazepines

The provision of long-term opioid analgesic therapy for chronic pain requires a careful risk/benefit analysis followed by clinical safety measures to identify and reduce misuse, abuse, and addiction and their associated morbidity and mortality. Multiple data sources show that benzodiazepines, prescribed for comorbid insomnia, anxiety, and mood disorders, heighten the risk of respiratory depression and other adverse outcomes when combined with opioid therapy. Evidence is presented for hazards associated with coadministration of opioids and benzodiazepines and the need for caution when initiating opioid therapy for chronic pain. Clinical recommendations follow, as drawn from 2 previously published literature reviews, one of which proffers 8 principles for safer opioid prescribing; the other review presents risks associated with benzodiazepines, suggests alternatives for co-prescribing benzodiazepines and opioids, and outlines recommendations regarding co-prescribing if alternative therapies are ineffective.     

Postherpetic Neuralgia: The Never-Ending Challenge

Abstract: Postherpetic neuralgia (PHN) is defined as pain that persists 1 to 3 months following the rash of herpes zoster (HZ). PHN affects about 50% of patients over 60 years of age and 15% of all HZ patients. Patients with PHN may experience two types of pain: a steady, aching, boring pain and a paroxysmal lancinating pain, usually exacerbated by contact with the involved skin. Herpes zoster is initially a clinical diagnosis, based on the observation of a typical dermatomal distribution of rash and radicular pain. HZ is pathologically characterized by inflammatory necrosis of dorsal root ganglia, occasionally associated with evidence of neuritis, leptomeningitis, and segmental unilateral degeneration of related motor and sensory roots. Although acyclovir has been used successfully as standard therapy for varicella zoster virus (VZV) infection in the past decade, resistant strains of VZV are often recognized in immunocompromised patients. Therapy with acyclovir and the use of corticosteroids have been reported to prevent PHN in up to 60% of HZ patients. Management of chronic pain in PHN is more problematic. The only therapy proven effective for PHN in controlled study is the use of tricyclic antidepressants, including amitriptyline and desipramine. There is good evidence of efficacy from randomized trials that gabapentin and pregabalin (new anticonvulsant drugs) are of benefit in the reduction of pain from PHN. As alternative therapies, topical agents such as capsaicin, lidocaine or opioid analgesic treatment may give satisfactory results. Interventions with low risk, such as transcutaneous electrical nerve stimulation (TENS), are appropriate. Evidence is scant for the value of surgical and procedural interventions in general, although there are numerous, small studies supporting the use of specific interventions such as nerve blocks, neurosurgical procedures, and neuroaugmentation. Although antiviral agents are appropriate for acute HZ, and the use of neural blockade and sympathetic blockade may be helpful in reducing pain in selected patients with HZ, there is little evidence that these interventions will reduce the likelihood of developing PHN. Postherpetic neuralgia remains a difficult pain problem. This review describes the epidemiology and pathophysiology of PHN and discusses proposed mechanisms of pain generation with emphasis on the various pharmacological treatments and invasive modalities currently available.     

Acute Pain and Availability of Analgesia in the Prehospital Emergency Setting in Italy: A Problem to be Solved

Objectives:   The treatment of acute pain in the prehospital emergency setting remains a significant problem. We evaluated the incidence, site, and possible cause of acute pain in the prehospital period and also the current state of prehospital pain management by evaluating analgesic availability in emergency vehicles in Italy.
Methods:   First aid volunteers documented the presence, intensity, and site of acute pain by questionnaire for over 3 months. Emergency service operations completed a questionnaire on analgesic availability in ambulances and helicopters.
Results:   Pain symptoms were present in two-thirds of the patients ( n  = 383) and ranked as moderate to unbearable in 41.75%. Results of the analgesic availability survey indicate that 10.6% of the ambulance services carry no pain killers (including non-steroidal anti-inflammatory drugs [NSAIDs] and/or paracetamol) and 11.5% are without an opioid. The emergency helicopter survey showed a significant difference in analgesic availability compared with ambulances, with 97.6% having at least one opioid agent available (weak or strong). A wide geographical variation in the availability of analgesic agents in ambulance and helicopter services was seen.
Conclusions:   There is a high prevalence of pain among patients receiving prehospital emergency treatment in Italy and treatment for acute pain during emergency treatment of trauma patients is inadequate. All emergency vehicles, without distinction, should carry opioids and other analgesic drugs (NSAIDs and paracetamol) and there should be no geographic differences in the availability of pain medications.     

镇痛药物及其应用

镇痛药物是医生们进行疼痛治疗的重要工具。镇痛药物根据作用机制可分为阿片类镇痛药、非阿片类镇痛及辅助性镇痛药。阿片类镇痛药以吗啡、芬太尼等为代表药物,近来其他人工合成的可待因衍生物如羟可酮、氢可酮等也逐渐被用于临床。非阿片类镇痛药物主要包括非甾体类抗类药,其中环氧化酶-2抑制剂如塞来昔布等高选择抑制剂具有副作用较小的优点。此外氯胺酮、可乐定等非阿片类药物的镇痛作用近来也被重新研究和应用。辅助性镇痛药物以抗惊厥、抗精神病药物为主,对于阿片类药物不敏感的患者,可作为辅助用药。     

Levetiracetam as an adjunctive analgesic in neoplastic plexopathies: case series and commentary

Certain types of pain associated with cancer may be difficult to treat with standard therapies, often resulting in intractable pain and suffering for the patient. The use of an opioid as analgesic monotherapy can lead to poorly controlled pain as well as multiple side effects. Non-opioid adjunctive analgesics, such as antidepressants and antiepileptic drugs (AEDs) often improve both pain control, and side effect prevalence. Levetiracetam is an AED with unique mechanisms of action that may have analgesic properties in various pain syndromes. Seven patients with neoplasms involving neural structures (four invading the brachial plexus, and three the lumbosacral plexus) had severe pain of 8 to 9 out of 10 on a visual analog scale (VAS), despite the use of parenteral opioids and various adjunctive therapies. These patients were treated with oral levetiracetam titrated over days to two weeks, depending on the location of pain, drug response, and tolerance to tapering of opioid analgesics. Opioid and adjunctive analgesic use and VAS scores were recorded periodically. The maximum levetiracetam dose ranged from 500 mg to 1500 mg BID. All patients experienced pain control improvement after the addition of levetiracetam, with VAS scores decreasing from 8-9 out of 10 to 0-3 out of 10 within two to 14 days of therapy initiation. Overall opioid use decreased by at least an estimated 70%, without drug related adverse events. In this small series of patients, levetiracetam effectively and safely improved pain relief in patients with neoplastic plexopathies previously resistant to standard analgesic approaches.