Barbara St. Marie, MA, ANP, GNP PhD Candidate University of Wisconsin – Milwaukee Nurse Practitioner – Supervisor Pain and Palliative Care – Fairview Ridges.

Barbara St. Marie, MA, ANP, GNP PhD Candidate University of Wisconsin Milwaukee Nurse Practitioner Supervisor Pain and Palliative Care Fairview Ridges Hospital

Objectives: Basic Neurophysiology of Pain Pathways Pharmacological and Non-pharmacological Interventions of Pain Pathways Matching neurophysiology with pharmacology Pathophysiology of Pain When Pain becomes Chronic or Persistent Pain Interventions of Chronic or Persistent Pain Nursing Contributions to Pain Management

Combination Analgesics Rationale Multimodal analgesia Multiple sites of action target multiple pain pathways Complementary pharmacokinetic activity Potentially synergistic analgesic effect Reduced adverse event profile with comparable efficacy Raffa, RB, 2001

Pain Process The neural mechanisms by which pain is perceived involves a process that has four major steps: Transduction Transmission Modulation Perception

Facilitating Transduction Biochemical mediators: Chemical Soup Prostaglandins Bradykinins Serotonin Histamines Cytokines Leukotrienes Substance P Norepinephrine

Peripheral Excitatory Mediators (Pain) SubstanceReceptorMechanism Substance P (SP) NK 1 neuronal excitability, edema Prostaglandin(PG)? Sensitize nociceptors, inflammation, edema Bradykinin B 2 (normal) B 1 (inflammation) Sensitize nociceptors PG production Histamine H1H1H1H1 C-fiber activation, edema, vasodilatation Serotonin 5-HT 3 C-fiber activation, release SP Norepinephrine(NE) 1111 Sensitize nociceptors Activate nociceptors

Peripheral sensitization Peripheral opioid receptors Management of histamine

Diclofenac

Acetaminophen (Tylenol) Analgesic, antipyretic Inhibits prostaglandin synthetase in the CNS, weak peripheral anti-inflammatory activity Serotonergic effect at descending pathway Used to treat osteoarthritis

Acetaminophen (Tylenol) American Pain Society: Maximum dose 4,000 mg/day, American Liver Foundation: 3,000 mg/day Risk of hepatotoxicity with higher doses Antidote acetylcysteine (Mucomyst, Acetadote)

Transmission of pain Defined as: Projection of pain into the Central Nervous System

Transmission A synapse contains three elements: the presynaptic terminal the synaptic cleft the receptive membrane

Transmission The presynaptic terminal is the axon terminal of the presynaptic neuron Here that the presynaptic neuron releases neurotransmitters which are found in vesicles

Capsaicin Hot peppers May deplete & prevent re- accumulation of substance P in primary afferent neurons responsible for transmitting painful impulses from peripheral sites to the CNS. Absorption, distribution, metabolism & excretion, half life unknown May produce transient burning with application, usually disappears in 2-4 days, but may persist for several weeks.

Transmission The synaptic cleft is the narrow intercellular space between neurons. Neurotransmitters cross the synaptic cleft and bind to specific receptors on the postsynaptic neurons This will excite or inhibit the postsynaptic neurons.

Muscle Pain Correlated with Lactic acid levels Lactic acid levels in the blood vessels of the muscle influence neuronal noxious stimuli What might that tell us about intervening with muscle pain?

Neuropathic Pain Features Burning, prickling, tingling Shock-like May or may not be lancinating Paresthesia May be associated with Allodynia Hyperalgesia Hyperethesia Referred Pain More intense at noc

Local Anesthetic Agents On-Q delivery Synera patch (topical) Emla: Lidocaine and Prilocaine 1:1 (topical) LMX 4% lidocaine (topical)

Local Anesthetics Blocks conduction of nerve impulses by decreasing or preventing an increase in the permeability of excitable membranes to Na+. Inhibits depolarization of nerve Blocks neuronal firing Challapalli, V., et. al., 2005

Lidoderm 5% Patch

Mentholatum Menthol generates analgesic activity through: Ca 2+ channel blocking activity Binding to kappa opioid receptors Stanos, S.P., 2007

Methyl Salicylate Toxicity Salicylic acid derivative (a.k.a. wintergreen oil, sweet birch oil) Lipid solubility increases toxicity More toxic than aspirin 1 teaspoon (5ml) wintergreen oil contains 4,000 mg salicylate 30ml wintergreen oil is a fatal dose in adults Risk of toxicity reduced with use for acute pain, limited to a small area of dermal application Chyka, P.A., et al., 2007

Anticonvulsants 1) Inhibit sustained high-frequency neuronal firing by blocking Na+ channels after an action potential, reducing excitability in sensitized C-nociceptors. 2) Blockade of Na+ channels and increase in synthesis and activity of GABA, in inhibitory neurotransmitter, in the brain. 3) Modulates Ca+ channel current and increases synthesis of GABA. Deglin, J.H. & Vallerand, A.H., 2001

Antiepileptic Agents Broad clinical actions in the CNS: Reduce seizures Neuropathic pain Bipolar disorder Anxiety Schizophrenia Agitation Impulse dyscontrol Dementia Delirium Three proposed mechanisms of action: Blockade of voltage gated sodium channels ( glutamate release) Blockade of voltage gated calcium channels alpha 2 delta subunits (reduces excessive neurotransmitter release) Enhancement of GABA actions

Lyrica Pregabalin Schedule V

Modulation Sympathetic Chain ganglion Substantia gelatinosa Post synaptic jct Contralateral spinothalamic

Ascending Pain Pathways Ascending fibers

Perception Review: Impulses go through the postsynaptic junction Cross the dorsal horn To the spinothalamic tract

Meperidine (Demerol) Duration 2-3 hrs PO doses 1/4 analgesic effect Toxic metabolite - normeperidine dysphoria, irritability, seizures t 1/2 =12-15 hrs; not reversible with Narcan Do not use Demerol for more than 48 hrs or at doses >600 mg/24hr Only indications: rigors, short term use, i.e. endoscopy.

Reference: Am Family Physician, 71(7), 2005 Methadone FDA Indications: Severe pain, narcotic detoxification, and temporary maintenance of narcotic addiction

Methadone Inexpensive Accumulates with repeated dosing 85% protein bound Slowly released up to 10 days after dose increase Available in 10 mg tablet or oral solution, use of 40 mg diskette no longer available for pain mgt use Patient may be subjected to scrutiny, stigma & misconceptions

Federal Regulation Prevention of withdrawal in opioid addiction Special annual registration with DEA Use only in an established addiction treatment program Maintenance patients may continue tx when admitted to acute care facility Treatment for pain Any clinician licensed to prescribe Schedule II drugs may prescribe methadone for pain

Methadone Incomplete Cross-Tolerance Inverse relationship with dosing Monitor ekg for QT prolongation

Schmittner, J., 2006 Clinical Indications for Electrocardiogram in Patients Receiving Methadone History of long-QT syndrome or torsades de pointes Family history of long-QT syndrome or early sudden cardiac death Cardiac arrhythmia and heart block (2 nd or 3 rd degree AV block) Anorexia nervosa Frequent electrolyte depletion (K, Ca, Mg) HIV patients on multiple-antiretroviral therapy Methadone dosages greater than 150mg/day Initiation of a P-450 inhibitor Initiation of medications associated with QTc prolongation Presyncopal or syncope symptoms Unexplained tonic-clonic seizures with abnormal electroencephalogram

Routhier, D., et al., 2007

Methadone Black Box Warning Deaths during initiation and conversion from other opioids Respiratory depression chief hazard Use of concomitant sedatives including alcohol Self-titration iatrogenic overdose QTc prolongation

Key Teaching Points Careful of mix up between long acting and short acting with same mg amount (ex. MS Contin and MSIR) Remove old patch before new one put on Safe disposal issues Drinking, driving issues Tell all of your healthcare providers everything that you take, always Careful about buying on the Intranet Sleepers, sedatives Teach S & S of withdrawal

Key Teaching Points Never take more or less than prescribed without calling us Only you take your pain medication, do not share! Never alter the medication, i.e. splitting sustained release medications Keep in a safe place always! Medication parties Middle & High School students; #1 medicine cabinet thefts Inciardi, J.A., et al., 2007

Some of our biggest safety issues Careful of look alike names and sustained release versus immediate release Only witness waste when you see it first, protect your hard earned license Careful of which line is which PCA pumps; double check, double check and double check-settings and syringe concentration, medication and document Instruct patient only to press button ISMP, February 2007

Descending Pathway Anatomic path From cerebral cortex Brain stem To dorsal horn Pain inhibition Enkephalin excites inhibitory interneurons in the dorsal horn

Descending Pathway Mediates voluntary and involuntary motor control Regulates somatic sensory processing Regulates the autonomic nervous system

Coexisting CD and Pain Unique experiences Anatomic paths of the nervous system have commonalities Addictive responses are altered by the physiological presence of pain Pain responses are altered by the physiological presence of addiction.

Endocannabinoids Research on the adaptations of cells continue with the recent discover of the cannabinoid receptor and the subsequent searching and findings of the endogenous cannabinoids. Two endocannabinoids, anandamine and 2- arachidonyl glycerol or 2-AG.

Endocannibinoids Found in most brain function Equal balance between endocannibinoids and their receptors occur (Fride, 2005) Role in brain plasticity leading to long term effects on movement and coordination habit formation reward and addiction

Opioid-Induced Pain Hypersensitivity Opioids may produce abnormally heightened pain sensations May share mechanisms with antinociceptive tolerance Possibly dose related? Observed both with acute and chronic use Current research indicates potential for targets for new therapies

Questions

Nursing Research in Pain Management Peggy Compton, PhD, RN Pain and Addiction Christine Miaskowski, PhD, RN Gender and Pain Christine Kovach, PhD, RN Elders and Pain Margo McCaffrey, MSN, RN Pain is what the patient says it is Betty Morgan, PhD, RN Pain and Addiction

Nursing Research in Pain Management Rosemary Polomano, PhD, RN Pain, Rat lab Keela Herr, PhD, RN Geriatric Pain Jo Eland, PhD, RN Pediatric Pain Donna Wong, PhD, RN Smiley Faces, Faces Scale for Pain assessment

What is Flare of Pain? Same Pain as Chronic (Persistent) Pain Same Location as Chronic (Persistent) Pain Different Pain Intensity from Chronic (Persistent) Pain Temporary increase in pain intensity from a more stable baseline pain with otherwise similar characteristics.

Pain Flare Study 2001-2002 Pain Flare Study Descriptive study N= 67 Location: University of Minnesota Fairview Pain Management Center Survey mailed to 75 patients, 67 responses IRB approval

Pain Flare Study Purpose of study Describe the characteristics of and factors contributing to pain flares in patients with chronic pain who receive care from the nurse practitioner in Fairview Pain Management Center

Conclusions Pain Flare definition: Same Pain, same location, different intensity This definition implies that Pain flare should not represent new pathology Patient has an ongoing pain problem that has been relatively stable No presumption of what baseline pain intensity was

Conclusions Studying flare gives meaning to the patients experiences of flare of their pain Gave patients a voice Assurance that it is not permanent condition Universality of flares in chronic pain Pain intensity rating less important in chronic non- malignant pain than changes in pain intensity Once contributing factors to pain flares have been resolved, chronic pain returns to baseline

Envision the Future Better pain control with fewer side effects Genome pain management Helping the brain erase persistent pain Social Policy that enhances comprehensive approach to pain management rather than reinforce procedures to get rid of pain Abuse deterrent opioid formulations that significantly reduce diversion and are available for those who need it.

Barbara St. Marie, MA, ANP, GNP PhD Candidate University of Wisconsin – Milwaukee Nurse Practitioner – Supervisor Pain and Palliative Care – Fairview Ridges.

Documents

pain management slide

acetadote slide

osteoarthritis slide

diclofenac slide

transmission of pain

receptive membrane slide

projection of pain

central nervous system