A symposium entitled “Paradigms in Pain: Current Mechanisms and Emerging Strategies” was presented on February 21, 2003, at the 19th Annual Meeting of the American Academy of Pain Medicine in New Orleans, LA. Topics of discussion included the underlying mechanisms of pain processing, current approaches to pain management, and multimodal and perioperative analgesia.

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Educational Objectives
Upon completion of this activity, participants should be able to:

• Review pain mechanisms.
• Consider current and potential therapeutic targets for pain management.
• Evaluate current therapy for pain.
• Highlight areas of unmet clinical need.
• Assess the potential benefits of multimodal analgesia.
• Discuss the impact of new approaches on pain management.

CME Accreditation
Paradigms in Pain: Current Mechanisms and Emerging Strategies
CME Consultants, Inc.
www.cmeconsultantsinc.com

A nationally accredited continuing medical education company sponsors this CME-accredited program.

Accreditation Statement for Physicians:
CME Consultants, Inc. is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Designation:
CME Consultants, Inc. designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.


Dates:
Date of original release: July 1, 2003
Valid for CME credit through: July 1, 2004

Disclosure:

CME Consultants, Inc. holds the standard that its continuing medical education programs be free of commercial bias.



Now, in accordance with the disclosure policy of CME Consultants, Inc., as well as standards set forth by the ACCME, the author has been asked to disclose any relationship he has to companies producing pharmaceuticals, medical equipment, prostheses, etc., that might be germane to the content of the lectures. Such disclosure is not intended to suggest or condone bias in any presentation, but is elicited to provide registrants with information that might be of potential importance to their evaluation of a given talk.


The following speaker has reported receiving something of value* from a company whose product may be germane to the content of this presentation:


Name: Mark J. Lema, MD, PhD

Company and Relationship
Merck & Co., Inc.: Speaker’s Bureau and Consultant
Presentation will include a discussion of Coxibs/NSAIDs for chronic preemptive pain.

* “Something of value” refers to an equity position, receipt of royalties, consultantship, funding by a research grant, receiving honoraria for education services elsewhere, or to any other relationship to a company that provides sufficient reason for disclosure, in keeping with the spirit of the stated policy.


Acknowledgment:
This activity is supported by an unrestricted educational grant from Merck & Co., Inc.


Paradigms in Pain: Current Mechanisms and Emerging Strategies
Spinal Systems and Pain Processing: Insights into Physiology and Pharmacology

When tissue is subjected to an acute, high-intensity stimulus, both animals and humans perceive pain and attempt to escape from the stimulus. This acute effect is mediated by the activation of small, high-threshold, slow-conducting primary afferents, whose frequency of discharge is proportional to the intensity of the stimulus. A group of second-order neurons are then activated, and their discharge frequency is also proportional to stimulus intensity.

If tissue is inflamed, the pain can be ongoing, even after removal of the original noxious stimulus. Until recently, it was believed that the mechanism of pain activation by more moderate stimuli involved peripheral or injury-site release of active factors that sensitize and stimulate activity in the primary afferents. It is now known, however, that ongoing afferent traffic causes processing in the dorsal horn of the spinal cord, leading to sensitization.1,2

The Facilitatory Cascade
An important component of this process is the cascade resulting from persistent afferent activity. This ongoing activity causes several transmitters to be released, including excitatory amino acids such as glutamate, and peptides like substance P. Following acute stimulation, glutamate activates an ionophore receptor (AMPA receptor). However, when afferent traffic is ongoing, this second-order neuron is depolarized, leading to activation of another ionophore receptor, the N-methyl-D-aspartate (NMDA) receptor. Substance P also activates the neurokinin-1 receptor. The activation of the NMDA and neurokinin-1 receptors results in increased intracellular calcium in dorsal horn neurons, activating the enzyme phospholipase A2. Phospholipase A2 in turn causes release of arachidonic acid, which is converted to prostaglandin by cyclooxygenase-2 (COX-2). The release of prostaglandin activates a variety of prostaglandin receptors that sensitize the primary afferent terminal, causing further transmitter release with stimulation and enhancing the excitability of the second-order neuron.3

In the early 1990s, it was observed that there are two distinct COX isoforms: COX-1 is constitutively (stably) expressed in peripheral tissue, and COX-2 is upregulated in the presence of inflammation.4 COX-1 and COX-2 are both constitutively present in the spinal cord, but recent work has suggested that constitutively expressed spinal COX-2 plays a predominant role.


Approaches to Therapy
Several therapeutic modalities are available, and different drug classes modulate different components of the facilitatory cascade. Opioids have presynaptic receptors on the primary afferent and on the second- order neuron. Opioids reduce terminal excitability by blocking information processing through this synapse and, thus, prevent response to acute nociceptive stimuli by raising the threshold of response. Inflammatory hyperalgesia can also be blocked by opioids preventing afferent input into the dorsal horn.5 Agents such as gabapentin that have no effect on acute pain processing can reduce inflammatory hyperalgesia by blocking the facilitatory cascade. Gabapentin may be useful preoperatively to decrease central sensitization. Nonselective COX inhibitors (nonsteroidal anti- inflammatory drugs [NSAIDs]) and COX-2 selective inhibitors interrupt the cascade and prevent central sensitization. Both effectively reduce pain by blocking the upregulated COX-2 enzyme present in hyperalgesia.

Since different drugs affect different aspects of the pain cascade, it should follow that clinicians might be able to use two or more drugs that may work synergistically at different sites, and that this might facilitate use of lower doses of all of the drugs being used. For this to be accomplished effectively, the nature of the interaction between different drugs must be known. For instance, in experiments using rats, morphine and a COX-2 inhibitor delivered together demonstrated potent additive interaction such that the dose of each could be halved. This synergy has been demonstrated in various models ranging from severe inflammation, such as the carrageenan model, to moderate inflammation, such as that produced by a crush injury, to modest inflammation, such as on the Formalin test (Figure 1).

Other research with rats has indicated that the use of COX-2 inhibitors before the infliction of tissue injury may block the activation of COX, and thus prevent initiation of the hyperalgesic state completely, whereas the same dose of drug given just 5 minutes after injury has less effect. These findings provide support for the use of preemptive analgesia before surgical procedures.

References
1. Mannion RJ, Woolf CJ. Pain mechanisms and management: A central perspective. Clin J Pain 2000;16(3 suppl):S144-S156.
2. Costigan M, Woolf CJ. Pain: Molecular mechanisms. J Pain 2000;1(3 suppl 1):35-44.
3. Svensson CI, Yaksh TL. The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol 2002;42: 553-583.
4. Hinz B, Brune K. Cyclooxygenase-2: 10 years later. J Pharmacol Exp Ther 2002;300:367-375.
5. Nozaki-Taguchi N, Yaksh TL. Spinal and peripheral mu opioids and the development of secondary tactile allodynia after thermal injury. Anesth Analg 2002;94(4):968-974.



Current Approaches to Pain Management: A Need for Improvement

In clinical practice, the distinction between acute pain caused by trauma and that caused by surgery is indistinguishable in terms of response; the body reacts to both wounds and surgical incisions as noxious stimuli. Unrelieved acute pain can have numerous negative sequelae, including significant, long-lasting morbidity and psychological stress (Figure 2). Despite this fact, a recent Gallup poll revealed that less than half of all surgical patients reported receiving satisfactory postoperative analgesia.1 This translates to approximately 21 million individuals experiencing unnecessary suffering in 1 year.

Since it can be assumed that physicians do not withhold relief out of malice, one must then conclude that administration of adequate analgesia is restricted because of possible adverse effects or limited efficacy. It is apparent, therefore, that approaches to treating pain, including postoperative pain, must be improved.

General Anesthesia and Chronic Pain
Contrary to popular belief, general anesthesia is not general analgesia and does not necessarily preclude the development of chronic postoperative pain. Although the patient is not aware of noxious stimuli during anesthesia, peripheral and subsequently central sensitization continue to develop, leading to possible long-term pain syndromes.2 In fact, it has been reported that more than 80% of amputees experience phantom limb pain and that over half of the patients experience post-thoracotomy and post-mastectomy pain for many months after these procedures. Both immediate postoperative pain and the psychological vulnerability that can be caused by pain have been cited as predictive of chronic pain.3

Current Pharmacologic Therapies for Pain
Pain therapies currently available are listed in the Table. A variety of drugs are used, including some that are not indicated for treating pain. Topical agents are being used in acute and chronic pain. Several types of creams are in use, including capsaicin and creams containing NSAIDs or local anesthetics. The principle behind most of these products is to apply a mildly irritating agent that would cause vasodilation and pave the way for better absorption of the drug.

Acetaminophen, although often used postoperatively, may actually be better suited to treat conditions such as arthritis. A question that needs resolution is how well agents such as NSAIDs and COX-2 inhibitors are absorbed into the central nervous system. NSAIDs have been shown to have a ceiling effect, so increasing dosages beyond a certain point does not increase their analgesic efficacy,4 and that limits their use in acute postoperative pain. Some COX-2 inhibitors have been shown to be absorbed sufficiently into the central nervous system to allow them to provide effective pain relief.5 Because acetaminophen does not inhibit COX-1 or COX-2, it has been thought that it might interact with a purported COX-3 isoenzyme.

The greatest problems with the nonspecific NSAIDs are their well-known gastrointestinal (GI) and bleeding side effects. These adverse effects are particularly troublesome for older patients. In one study, a 200% increase in operative and postoperative blood loss was observed in patients given NSAIDs.6 The cost of therapy with a COX-1 inhibitor is often increased by the need to add a proton pump inhibitor or other GI-protective drug. In addition to bleeding and GI effects, NSAIDs have been observed to cause hypertension and renal adverse events.7,8

The advantage of the COX-2–specific inhibitors is their safety profile, which is superior to that of the nonspecific NSAIDs with no loss of efficacy. In addition to peri- and postoperative bleeding, another issue with NSAID use involves possible inhibition of bone remodeling. In a retrospective 1998 study, ketorolac had a significant negative effect on spinal fusion: 29 of 167 patients given ketorolac had nonunions, whereas only 5 of 121 patients who did not receive any NSAIDs had nonunions.9 Recent studies with rofecoxib showed similar nonunion rates in patients treated with rofecoxib to those in untreated controls.10 This suggests that inhibition of remodeling may primarily be a problem with nonspecific drugs but not with COX-2–specific inhibitors; however, there have been no head-to-head trials to date.

Opioids are being used increasingly to treat chronic nonmalignant pain.11 However, opioid side effects are problematic, and patients often stop taking drugs because the adverse effects are worse than the untreated pain. Various combinations of opioid and nonopioid analgesics have been tried, heralding the genesis of the multimodal approach. The coadministration of a non­opioid analgesic can have an opioid-sparing effect and reduce opioid side effects.


Preemptive Analgesia
Traditional postoperative analgesia is provided as a reaction to a need. Although effective postoperative pain relief speeds recovery and reduces complications, it is not achieved by many patients. Barriers to effective postoperative pain relief include:

• Patient/family/physician fear of addiction
• “The good patient doesn’t complain” syndrome
• Concern about side effects
• As-needed (prn) dosing that is administered too late
• Imprecise dosing direction that is interpreted most conservatively
• Low priority given to pain management in hospitals

• Concern with government restriction of opioid use

The underlying principle of preemptive analgesia is to treat prior to the onset of pain, rather than in reaction to it.12 An early study demonstrated that preoperative lumbar epidural blockade in patients undergoing limb amputation significantly reduced the incidence and duration of phantom limb pain.13 Only three of 11 patients who received preoperative epidural blockade had phantom limb pain, compared with nine of 14 patients who did not receive preoperative blockade. After 1 year, all patients who had received preoperative blockade were pain-free, whereas three patients in the control group were still experiencing phantom limb pain.

Preoperative analgesia may not be sufficient to control perioperative pain, and consideration should be given to a multimodal approach involving agents that work synergistically to prevent pain and are given perioperatively and long term to prevent the development of chronic pain.


References
1. Gallup Poll, 1995.
2. Mannion RJ, Woolf CJ. Pain mechanisms and management: A central perspective. Clin J Pain 2000;16(3 suppl):S144-S156.
3. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery: A review of predictive factors. Anesthesiology 2000;93:1123-1133.
4. Mercadante S. The use of anti-inflammatory drugs in cancer pain. Cancer Treat Rev 2001;27:51-61.
5. Buvanendran A, Kroin JS, Luk P, et al. Blood-brain barrier penetration of oral rofecoxib, a selective cyclooxygenase (COX-2) inhibitor, in dogs. Anesthesiology 2002;96:A465.
6. Robinson CM, Christie J, Malcolm-Smith N. Nonsteroidal antiinflammatory drugs, perioperative blood loss, and transfusion requirements in elective hip arthroplasty. J Arthroplasty 1993;8:607-610.
7. Whelton A, Hamilton CW. Nonsteroidal anti-inflammatory drugs: Effects on kidney function. J Clin Pharmacol 1991;31(7):588-598.
8. Gurwitz JH, Avorn J, Bohn RL, et al. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory drug therapy. JAMA 1994;272(10): 781-786.
9. Glassman SD, Rose SM, Dimar JR, et al. The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 1998;23:834-838.
10. Reuben S. (Letter). Reg Anesth Pain Med 2001;93:803.
11. Przewlocki R, Przewlocka B. Opioids in chronic pain. Eur J Pharmacol 2001;429:79-91.
12. Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia II: Recent advances and current trends. Can J Anaesth 2001;48:1091-1101.
13. Bach S, Noreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988;33:297-301.


New Strategies in Perioperative Pain: Assessing the Benefits

Poorly controlled pain can lead first to peripheral sensitization and ultimately to central sensitization. Peripheral sensitization may cause increased wound sensitivity, heightened perioperative pain, and central sensitization to prolong disability and convalescence. If central sensitization is not controlled, chronic pain syndromes may develop (Figure 3), as is seen in a significant percentage of patients with acute pain.1

The realization that peripheral and central sensitization can occur postoperatively as analgesic effects wear off has suggested the need for a new strategy to optimize pain control. Preemptive analgesia was adopted to address the ongoing inflammation and movement-associated aggravation of tissue injury that was seen after surgery. The most recent model, however, also uses perioperative and postoperative analgesia, in addition to preemptive analgesia, in an almost seamless continuum of pain control.


Multimodal Analgesia
Multimodal, or balanced, analgesia is the use of several drugs to block pain at various sites in the peripheral and central nervous system. This approach takes maximum advantage of the benefits of each component while minimizing the possible adverse effects that can result from high-dose monotherapy with a single agent such as an opioid. Although opioids provide very effective pain relief, they often have a variety of troubling side effects that can range from bothersome to life-threatening, can prolong hospital stays, and can cause patients to stop taking them, thereby forfeiting pain control.2 In a multimodal approach, the patient’s exposure to these adverse effects is reduced.

There are several stages in cellular pain processing and several effective agents that may be used at each stage:

• Transduction is activation by prostaglandin, histamines, and other mediators of the primary nociceptive nerve ending following a pain stimulus. Drugs that are effective in blocking transduction include nonselective NSAIDs, COX-2 inhibitors, antihistamines, and topical local anesthetics.
• Conduction of noxious impulses along the nerve axon can be interrupted with peripheral nerve blocks and local anesthetics.
• Transmission between the primary afferent nerve and the second-order neuron in the dorsal horn of the spinal cord can be stopped with neuraxial blockade, such as an epidural block with local anesthetics.
• The modulatory mechanism within the dorsal horn can be controlled with opioids, alpha-adrenergic agonists, and NMDA receptors, as well as with COX inhibitors.
• Pain perception in the sensory and limbic cortex is reduced by opioids, acetaminophen, and clonidine. The role of low-dose ketamine is also being re-examined in this setting.
• Responses to pain in the central nervous system can be attenuated with various agents. Muscle-relaxing drugs like benzodiazepines can control spasms. Also useful are tricyclic antidepressants and gabapentin (which may have utility in both chronic and acute pain), when the pain is primarily neuropathic in nature.

Efficacy of Preemptive Analgesia
There have been some excellent clinical trials demonstrating the benefits of preemptive analgesia before surgery. In one placebo-controlled trial, rofecoxib was administered to patients undergoing arthroscopic knee surgery.3 All patients were sedated and given local anesthesia. One-third of the patients also received 50 mg of rofecoxib 1 hour before surgery, one-third received 50 mg of rofecoxib right after surgery, and a third group received placebo before surgery. The duration of analgesia, defined as the time from the end of surgery to first opioid use, was 803 ± 536 minutes in the patients who received rofecoxib preoperatively, 461± 344 minutes in the group receiving postoperative rofecoxib, and 318 ± 108 minutes in the placebo group. Use of acetaminophen/oxycodone was also lower in the group receiving preoperative rofecoxib: 1.5 ± 0.6 pills in 24 hours versus 3.3 ± 1.3 pills in the group receiving postoperative rofecoxib, and 5.5 ± 1.6 pills in the placebo group. Pain scores were also lower in the group receiving preoperative rofecoxib. This was a dramatic illustration of the benefits of preemptive analgesia using COX-2–specific inhibition.3

In another double-blind, placebo-controlled study, 143 patients undergoing elective otolaryngologic surgery were randomized to receive placebo, 2 g of acetaminophen, 50 mg of rofecoxib, or 2 g of acetaminophen plus 50 mg of rofecoxib.4 The first dose of medication was given 15-45 minutes before surgery, and the second dose was given the morning after surgery. Premedication with rofecoxib was significantly more effective than placebo or acetaminophen in reducing peak postoperative pain and the need for analgesic medication, and in improving the quality of recovery and patient satisfaction. In this study, the addition of acetaminophen to rofecoxib did not improve efficacy (Figure 4).4

Ketamine, in addition to other effects, is an NMDA receptor antagonist. Given preoperatively in very low doses, this drug may significantly reduce postoperative pain and disability. A study with 100 patients undergoing surgery with combined epidural/general anesthesia assessed the efficacy of intraoperative ketamine in controlling postoperative pain.5 Patients received either a 0.25-mg/kg bolus followed by a 0.125-mg/kg/h infusion, a 0.5-mg/kg bolus followed by a 0.25-mg/kg/h infusion, a 0.25-mg/kg epidural followed by a 0.125-mg/kg/h infusion, or placebo. At the end of surgery, all patients were switched to patient-controlled analgesia with morphine. Both mechanical hyperalgesia and morphine requirements, measured out to 72 hours, were significantly lower in the higher-dose ketamine group than in the placebo group, as was residual pain followed out to 6 months after surgery.

Gabapentin is also being evaluated in the perioperative setting. In a double-blind study, 65 patients scheduled to undergo radical mastectomy were randomized to receive either a 1200-mg dose of gabapentin or placebo 1 hour before surgery.6 After surgery with general anesthesia, patient-controlled analgesia with morphine was provided. Use of morphine over 4 hours was 53% lower in the gabapentin group than in the placebo group, and pain upon movement was also reduced significantly at both 2 and 4 hours postsurgery in the gabapentin group.


Case Study: Multimodal Analgesia
A 63-year-old man with type 1 diabetes and chronic obstructive pulmonary disease was admitted for a Whipple procedure. The goal was to provide the best possible relief of what most likely would be severe pain, keeping in mind the patient’s respiratory limitations and high sensitivity to potent opioids.
A multimodal approach was adopted, beginning with preemptive use of 50 mg of rofecoxib given 1 hour before surgery. The next step was thoracic epidural injection with levobupivacaine and an opioid, in this case, hydromorphone. General anesthesia was used along with an intraoperative epidural infusion of diluted hydromorphone and levobupivacaine.
The patient awoke rapidly because anesthesia was light, and he took good breaths since his pain was well controlled. He was extubated and did well. The epidural infusion was continued for 48 hours. At that point, the epidural was discontinued and the patient was given controlled-release, low-dose oxycodone. Rofecoxib 50 mg/day was continued for 5 days, after which the dosage was decreased to 25 mg/day. Oxycodone was discontinued after 1 week. This multimodal approach, starting with preemptive analgesia, was very effective for this patient.


The New Paradigm
As our understanding of pain mechanisms expands, a new paradigm of pain management, based on perioperative and multimodal strategies, is formulating (Figure 5). Several drugs are being explored and developed as potential components of such strategies. Although ketamine has been shown to be useful preemptively, it most likely does not have a place in routine postoperative pain control. More selective NMDA receptor antagonists with less adverse side effects are needed. A new intravenous form of acetaminophen promises to be a powerful addition to the analgesic armamentarium. Effective doses of gabapentin are being established in research.

The COX-2 inhibitors, with their high degree of efficacy and excellent safety profiles, currently are considered an integral part of many multimodal analgesic strategies. Along with other nonopioid analgesics used perioperatively, COX-2 inhibitors have the potential to provide effective pain control and to allow potent opioid analgesics to be reserved for use in breakthrough pain. The new paradigm offers patients the possibility of a much less traumatic surgical experience.

References
1. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery: A review of predictive factors. Anesthesiology 2000;93:1123-1133.
2. Abbas SQ, Abbas Z. Is opiate compliance a problem in cancer pain? A survey of health care professionals’ views. Int J Palliat Nurs 2003;9(2):56-63.
3. Reuben SS, Bhopatkar S, Maciolek H, et al. The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002;94:55-59.
4. Issioui T, Klein KW, White PF, et al. Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Anesthesiology 2002;97:931-937.
5. De Kock M, Lavand’homme P, Waterloos H. ‘Balanced analgesia’ in the perioperative period: Is there a place for ketamine? Pain 2001;92:373-380.
6. Dirks J, Fredensborg BB, Christensen D, et al. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 2002;97:560-564.


This special report was produced by MultiMedia HealthCare/Freedom, LLC, and sponsored by CME Consultants, Inc., under an unrestricted educational grant from Merck & Co., Inc. The views expressed in this publication are not necessarily those of Merck & Co., Inc., CME Consultants, Inc., or the publishers. This publication may not be reproduced in whole or in part ­without the express written permission of MultiMedia HealthCare/Freedom, LLC.



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CME Examination

Paradigms in Pain: Current Mechanisms and Emerging Strategies
Please circle the letter of the correct answer for each of the following questions, and mail this page along with the Evaluation to CME Consultants, Inc., 94 Main Street, Wakefield, RI 02879.


1. In the facilitatory cascade, COX-2 synthesizes what produced from arachidonic acid?
a. Substance P
b. Neurokinin-l
c. Prostaglandin
d. Arachidonic acid


2. In the presence of inflammation, COX-____ is upregulated.
a. 1
b. 2


3. Less than half of all surgical patients report receiving adequate analgesia postoperatively.
a. True
b. False


4. General anesthesia blocks
a. sensitization to noxious stimuli temporarily.
b. sensitization to noxious stimuli permanently.
c. awareness of noxious stimuli temporarily.
d. awareness of noxious stimuli permanently.


5. Phantom limb pain is experienced by more than ______ of amputees.
a. 20%
b. 40%
c. 60%
d. 80%


6. If left untreated, acute pain most likely will fade away over time.
a. True
b. False
7. The use of nonspecific NSAIDs in treating acute postoperative pain is limited by
a. their gastrointestinal and bleeding side effects.
b. the “ceiling effect,” meaning that their efficacy does not increase dose dependently.
c. Both a and b
d. None of the above


8. Multimodal analgesia uses
a. multiple drugs all targeting the same point in the pain cascade.
b. multiple drugs each targeting a different point in the pain cascade.
c. a single drug used at different time points.
d. multiple drugs all used postoperatively.


9. The principle of preemptive analgesia is to
a. treat prior to the onset of pain to prevent or minimize it.
b. treat as soon as pain is noticed to keep it manageable.

c. treat once pain has become intolerable to try to reduce it.

d. None of the above


10. COX-2 inhibitors are useful components of a multimodal analgesic strategy because of
a. their high efficacy.
b. their good safety profile.
c. their cost-effectiveness.
d. All of the above


Answer Key
1. c
2. b
3. a
4. c
5. d
6. b
7. c
8. b
9. a
10. d


CME Evaluation

Paradigms in Pain: Current Mechanisms and Emerging Strategies
We would very much welcome your views on this program. To receive credit for this program, please complete the Evaluation, fill in your name and address, and mail this page along with the Examination to CME Consultants, Inc., 94 Main Street, Wakefield, RI 02879. Please allow 4-6 weeks for processing. Please phone (401) 789-4413 or fax (401) 789-4366 with any questions.


Learning Objectives Disagree Agree
Review pain mechanisms. 1 2 3 4 5

Consider current and potential therapeutic 1 2 3 4 5
targets for pain management.

Evaluate current therapy for pain. 1 2 3 4 5

Highlight areas of unmet clinical need. 1 2 3 4 5

Assess the potential benefits of multimodal 1 2 3 4 5
analgesia.

Discuss the impact of new approaches on 1 2 3 4 5
pain management.

Program/Topic
The extent to which this program met the 1 2 3 4 5
stated objectives

The overall quality of the activity 1 2 3 4 5

The applicability/usefulness of material 1 2 3 4 5
to your practice

The objectivity and fair balance of this 1 2 3 4 5
presentation (commercial vs educational)

The effectiveness of teaching strategies/ 1 2 3 4 5
presentation style

The overall format/organization of 1 2 3 4 5
the program

The overall knowledge of the faculty 1 2 3 4 5


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A supplement to Clinical Geriatrics and Annals of Long-Term Care