Most double-blind or single-blind studies investigating multimodal analgesia with a combination of nonsteroidal anti-inflammatory drug (NSAID) and opioid, with or without local anesthetic, show lower pain scores, a need for fewer analgesics, and prolongation of the time needed for postoperative analgesia compared with control groups. 1 Reference: 1. Jin F, Chung F. Multimodal analgesia for postoperative pain control. J Clin Anesth. 2001;13:524–539.
Chronic pain can be of mixed etiology with both nociceptive and neuropathic characteristics, as in some back pain conditions
Studies have demonstrated that patients with IBS have a heightened state of visceral sensitivity. 1 In 1980, Whitehead et al evaluated pain thresholds of a total of 25 IBS patients and 20 healthy controls. By distending a rectosigmoid balloon in a stepwise fashion, the investigators found that pain thresholds in IBS patients were significantly lower than in controls ( P <0.05). 2 Studies evaluating the pain thresholds of other GI disorders involving the esophagus 3 and stomach 4 have shown similar findings. References: 1. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut . 1973;14:125-132. 2. Whitehead WE, Engel BT, Schuster MM. Irritable bowel syndrome: physiological and psychological differences between diarrhea-predominant and constipation-predominant patients. Dig Dis Sci . 1980;25:6:404-413. 3. Richter JE, Barish CF, Castell DO. Abnormal sensory perception in patients with esophageal chest pain. Gastroenterology . October 1986;91:845-852. 4. Mearin F, Cucala M, Azpiroz F, Malagelada J-R. The origin of symptoms on the brain- gut axis in functional dyspepsia. Gastroenterology. October 1991;101:999-1006.
Functional magnetic resonance imaging (fMRI) data provide supporting evidence that FM is a central pain disorder and demonstrate the presence of cortical/subcortical pain processing in FM. 1 fMRI was used to evaluate cerebral activation patterns during the application of painful pressure in FM patients (n=16) and controls (n=16) 1 Each patient underwent fMRI while pressure was applied to the thumbnail bed; 13 regions of increased brain activation were revealed in the FM group, compared with 1 in the control group 1 The graph depicts pain intensity against stimulus intensity. In FM patients, a low stimulus pressure produced a high pain level; however, in stimulus pressure controls, a similar pressure resulted in low levels of pain 1 Enhanced responses were noted in multiple areas of the brain, including somatosensory primary and secondary cortex, insula, putamen, and cerebellum; this provides supporting evidence that CNS alterations may underlie FM pathophysiology 1 Reference: 1. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum . 2002;46:1333-1343.
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Multimodal Chronic Pain Treatment New Directions N. Lee Smith MD Center for MindBody Health Director, Stress Medicine Omega Pain Clinic and Lifetree Clinical Research Salt Lake City, Utah
Focus• Acute vs Chronic Pain• Nociceptive vs Neuropathic vs Central• The common role of central sensitization – Prototype: Fibromyalgia• Multimodality treatment: – How to reduce opiates with good relief?• Myofascial Trigger Points
Acute pain = a symptomChronic pain = a diseaseIf acute pain goes under-treated, more chronic pain
Chronic post-surgical pain• Thoracotomy 50-60%• Amputation 50%• Breast surgery 33%• Inguinal hernia 30%• C-section 12% Why? And who is more likely? How to prevent this?
Pain Treatment: How are we doing? “Pain can be relieved effectively in 90% of patients, but is not relieved effectively in 80% of patients” Walco, New Engl J Med 1994;331:8Chronic pain is often misunderstood
Acute pain is often inadequately treated: Why?• Fear of opiods: MD – 1/2 of fractures receive them – 42% come to ER for pain: • 3/4 leave in moderate to severe pain• Patient fears: 3/4 prefer non-opiate
What percent of chronic pain patients say,“Opiates give me little or no pain relief”? 53% American Pain Foundation Survey 2007
Distinguishing different types of pain Nociceptive Neuropathic Central Caused by nerve Caused by tissue damage Snsitization lesion or dysfunction • Arthritis • Fibromyalgia • Painful Diabetes • Injuries • Low back pain • Shingles, PHN • Postoperative pain • Neck pain • Sciatica • Trigeminal neuralgia
Pain Distribution • Use a body pain diagram • Have a patient color all areas of the body in which they feel painAdapted from pain drawing provided courtesy of L Bateman. Back Front
Neurotransmission Issues Inhibitory tracts (NE, DA, 5HT) When inhibition is lacking, the nervous system hypersensitizes SP
CSF Substance P in FMS4540353025 Normals20 FMS1510 5 0 Vaeroy Russell Welin Bradley
Fibromyalgia: Pain Processing Disorder fMRI Evidence: Augmentation fMRI = functional magnetic resonance imaging. Gracely et al. Arthritis Rheum. 2002;46:1333-1343.
FMS: Neurotransmission Abnormalities (in CSF)• Low central serotonin function } ⇒ deep sleep loss, anxiety)• Low central norepinephrine function ⇒ fatigue, pain, cognition ADs• Low dopamine function ⇒ ↓attention, ↓pleasure, ↓ sex, RLS }• High Substance P ⇒ pain amplification ACs• High Glutamate Russell J Arth Rheum 1994;37:1543-1560
Pharmacological Targets for Treatment Deep sleepAntidepressants (NRIs) Tramadol Inhibitory tracts Tapentadol (NE, DA & 5HT) Dopamine agonists NSAIDsIf present: Anticonvulsants, trigger SP neural stabilizers points?
Grading Pain Severity For example • Nuisance: after exercise aches • Distracting: menstrual cramps, OA, finger burn residual • Disabling: migraine, toothache • Worst Possible: labor, severe burns, kidney stone 50% 30%0___1____2____3____4_____5____6____7____8_____9___10 nuisancedistracting disabling worst
Neuropathic Pain: >50% Reduction 7 6 5 Na ACs(CBP,OXC)Number 4 TCAsneeded Tramadolto treat 3 Ca ACs(PGB,GBP) SNRIs(dulox,venla) 2 SSRIs 1 0 Na+ TCAs Tram Ca++ SNRIs SSRIs ACs ACs Gilron et al. CMAJ 2006;175(3) Cochrane Database SR 2006;3:CD003726
Anticonvulsants: Neural stabilizers• Sodium channel block (e.g., divalproex, lamotrigene)• Calcium channel modulation (e.g.,pregabalin, gabapentin)• GABA enhancers (e.g., tiagabine, baclofen)These ↓ Glutamate release Using meds with complementary mechanisms in lower dose may be better than high doses of one mechanism
Positive Pharmacological Trials for Fibromyalgia• Anticonvulsants: Pregabalin (30% get 50% improvement)• Dual action “antidepressants”: (30-40% get 50% improved) – Milnacipran, Duloxetine, Venlafaxine – Tricyclics (about 1/3 improve with low dose) – Cyclobenzaprine (10-30 mg) – Tramadol (28% reduction)• Dopamine agonists: (75% improve; about 40% get 50% improv.)• Gamma hydroxybuyrate (GHB) (30% get 50% improvement) Usually, these are used in combination
SNRIs for Pain• Duloxetine – FDA indicated in four types of pain• Minacipran – For fibromyalgia – More NE than serotonin
Tricyclics for Pain• Second generation: more NE; fewer side effects – nortriptylene – desipramine – cyclobenzaprine: better deep sleep (in low dose)
Opiates in Neuropathic Pain Meta-analysis of 22 studies (n=521) • Intermediate term (1+ months): – VAS reduction from placebo = 1.4 / 10 – No reduction in disability or mental health scores • In all but one study • Short term: Sometimes helpful (contradictory results ) Eisenberg E. JAMA 2005;293:3043-3052One opiate is FDA-approved for neuropathic pain: tapentadol
How to tell if opiate responsive? (Note well: Function)• Good initial response: use long acting opiod – Should be dose responsive• If poorly responsive after 2-3 titrations: Initiate an escape strategy• If initially partially responsive (“Taking the edge off”: change opiate, and other factors need addressing – Strongly consider an antihyperalgesic opiate
Two Anti-hyperalgesic Opiates:• Buprenorphine – Unique receptor profile – Patch = different dosing than SL• Tapentadol – Weak opiate + NRI – Indicated for both chronic pain and neuropathic pain These two appear to have less abuse potential
Myofascial Pain Syndrome: Treatment1. Inactivation of trigger points• Injection of local anesthetic (lidocaine + bipuvicaine) – Precision in placement of the needle a the point of maximal tenderness is essential – A local “twitch response” is usually obtained⇒Followed by vigorous massage and stretching
Myofascial PainSyndrome: Treatment2. Muscle Rehabilitation• Stretching, strengthening• Postural exercises• Movement: – massage, acupressure (strain/counterstrain) These maintain the gains
Myofascial Pain Syndrome: Treatment- Prevention3. Control of contributing factors:• Mechanical: Correct repetitive, tensing movements – Posture and lifting improvement• Aerobic exercise• Stress resilience: – Treat anxiety and depression – Experiential cognitive behavioral resilience training
Who is likely to get chronic pain ifacute pain treatment is suboptimal ?• Personal or family history of CNS hypersensitivity disorders – and sleep problems• History of abuse, trauma or childhood neglect high CRF and sympathetic tone For surgery in these, consider pre-emptive analgesia
Which Medication to Start?• Depends on dominant patterns of problems: – Sleep + pain + tingling + anxiety: Anticonvulsant – Pain + depression/anxiety + fatigue + cognitive: NSRI • R/O bipolar (Add sleep agent) – Pain alone: tramadol or cyclobenzaprine? – Fluctuating pain + mood/anxiety or anger: Anticonvulsant (± Atypical neuroleptic)Often, thoughtful combinations are best
Treating Chronic Pain Disorders Five important parts (interdisciplinary):• Treat early and aggressively• Treat CNS neurochemical hypersensitizing issues – Anticonvulsants (3 types), dual antidepressants, DA and alpha-2 agonists• Treat sleep well (particularly deep stages)• Carefully paced exercise• Treat “stress”: Experiential cognitive-behavioral methods• Consider trigger points• This reduces opiate requirements and improves function
Self Care Websites OFFER Organization for Fatigue and Fibromyalgia Education and Research http://www.offerutah.org/ University of Michigan Fibromyalgia Center Dr. D. A. Williams and Dr. M. Careyhttp://www.med.umich.edu/painresearch/patients/self.htm