1. Daniel Wermeling, Pharm.D. Professor 225 COP

2.  Nociception - the detection of tissue injury by peripheral nerve fibers  Pain – an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage  Pain requires recognition by higher centers in the brain

3.  Transduction/Stimulation  Activation of nociceptors from noxious stimulation such as heat, chemicals, trauma  Causes release of activators such as prostaglandins, Substance P, bradykinins, histamine and leukotrienes  Also possible activation of sympathetic nervous system (fight or flight), some pain nerve fibers pass through sympathetic ganglia

4. Transduction Prostaglandin Tissue Injury Overall effect is increased nociceptor activation Histamine NGF Bradykinin 5-HT ATP H+ Mediators Prostaglandins Leukotrienes Substance P Histamine Bradykinin Serotonin Hydroxyacids Reactive oxygen species Substance P Kelly D, et al. Can J Clin Anaesth. 2001;48:1000-1010. Pain: Current Understanding of Assessment, Management, and Treatments. Monograph developed by NPC and JCAHO, December 2001.

5.  Takes place on A-delta and C afferent nerve fibers  A-delta produce sharp localized pain sensations and are “fast”  C fibers produce dull, aching, poorly localized pain and are “slower”  Comprise the “first” pain from A (sharp) and “second” pain sensation from C fibers (dull, throbbing)  Example – hit thumb with a hammer

6. Reticular Formation Rostroventral Medulla Descending Pathway Spinal Cord Ascending Pathway Dorsal Horn Primary Nociceptive Fiber (A-  or C fiber) Inhibitory Transmitters GABA Glycine Somatostatin Descending Inhibitor Pathways Excitatory Transmitters Substance P Calcitonin gene  related peptide Aspartate, glutamate Kelly D, et al. Can J Clin Anaesth. 2001;48:1000-1010. Pain: Current Understanding of Assessment, Management, and Treatments. Monograph developed by NPC and JCAHO, December 2001.

7.  Nerve fibers enter dorsal horn of spinal cord  Message is transmitted via various tracts to higher centers in brain  Pain is then perceived consciously  Higher centers can influence or modify the pain experience  Anxiety, fear, relaxation, depression, rest, mood elevation, diversion & fatigue all influence the experience of pain  Rationale for Rx & non-pharmacologic treatments

10.  Central endogenous systems provide feedback to the spinal and afferent systems  Endogenous opiates - enkephalin, endorphins  Sympathetic system- norepinephrine, epinephrine  Other central inhibitory neurotransmitters  acetylcholine, serotinin, norepinephrine, neurokinins, etc.  Gate Control Theory of Pain Modulation  Non-nociceptive sensations such as heat, cold, vibration, touch, in same dermatome as the painful stimulus, reduces the sensation of pain. Spinal gate is closed by new signals

11.  Pain from damage to afferent nociceptive nerve fibers, not activation of peripheral receptors from stimuli  Syndrome results from continuous abnormal processing of sensory input and subsequent physiologic (plasticity) changes within the nervous system  Modulation and transmission functions become dysfunctional

12.  Some nerves degenerate and the lesions trigger  Expression of Na+ channels on damaged C-fibers  Expression of Na+, α -adrenoceptor on uninjured fibers  Promotes hyperexcitation and spontaneous nerve firing

13. Ca 2+ Glutamate C-Fiber Central Axon AMPA NMDA Substance P NK-I Na + K+K+ Ca2 + Mg2 + Plug Removed c-fos expression NO Synthase NO PKC Dorsal Horn Cell GABA B μ δ α2α2 5-HT 3 Baclofen Opioids Clonidine GABAA 5-HT1B K+K+ Guanyl Synthase Closed K + Channel Basbaum A. PNAS. 1999;96:7739-7743.

14.  Burning (like foot on a hot plate)  Tingling  Electrical shock, shooting and muscle spasms  Hyperalgesia – exaggerated painful perception to normally noxious stimulus (like a pin-prick)  Allodynia - Painful response to a non-noxious stimulus (rubbed by a feather)  Closest example of “hitting your funny bone”

16.  Endocrine/metabolic  Metabolic disturbances related to altered release of hormones, glucose intolerance, hypercortisolism  Cardiovascular  CV responses can cause unstable angina, myocardial infarction, deep vein thrombosis  Respiratory  May lead to atelectasis or pneumonia

17.  Gastrointestinal  May reduce gastric emptying and motility  Musculoskeletal  Impaired mobility and function  Immune system  Increased susceptibility to infection  Genitourinary system  May disturb urine output, fluid volume, and electrolyte balance  Nervous System - Untreated or under treated acute pain can lead to chronic pain condition

18.  Psychological effects of unrelieved pain  Feelings of anger, resentment, fear, anxiety, depression  Patients may consider or attempt suicide  Loss of enjoyment of life, feelings of social isolation  Conflicts in interpersonal relationships

19.  Impact on patients’ ability to function  Need assistance in daily living activities  Cannot participate in usual leisure or social activities  Difficulty in achieving restful sleep, which diminishes concentration and cognitive abilities and causes irritation

20.  Impact on patients’ ability to function  Many cannot work  25% quit job  20% take disability leave  17% had to change jobs

21.  In hospitals/clinics pain considered fifth “vital sign” to encourage regular assessment  JCAHO standards in hospitals  Must have routine SOPs for assessment and treatment  Consider the setting – out- vs in- patient, surgery, acute on top of chronic pain, etc.

22.  Patients’ right to pain management  Report will be believed  Response will be quick  Pain will be assessed and reassessed as needed  Patients will be educated about pain management  In the appropriate context  Inpatient  Ambulatory  Acute vs Chronic

23.  Patient considerations:  Onset, duration, location, quality, severity, intensity of pain  What alleviates or exacerbates the pain  How current treatment is working  Adverse effects of current treatment  Impact on function, behavior, mental status

24.  P = Palliative factors – what makes pain better? & Provocative factors – what makes it worse?  Q = Quality – Describe the pain in own words  R = Radiation – Were is the pain?  S = Severity/Intensity – How does the pain compare with other pain you have experienced  T = Temporal – Does the intensity change with time?

27.  History and Physical  Diagnostic Testing  Pain Specific Assessments  Patient Goals and Expectations  Create a Care Plan  Assess Patient and Environment Barriers  Presence/Absence of Aberrant Behavior

28. Age Body Habitus Other Diseases Organ Dysfxn Other Meds Cost and Insurance Evidence- based Guidelines Compliance Uncert- ainty Factors Life is like a box of chocolates – You never know what you are going to get – Forrest Gump, Philosopher Spin Here

29.  Categorical scales  Patients select from list of words or pictures showing pain  Especially helpful for use with children and cognitively impaired individuals  Multidimensional tools for Chronic Pain  Validated tools include questions about various aspects of pain and its effect on the patient’s life  More complex, time-consuming

30.  Disability index  Developed to assess pain’s effect on functioning  Walking, lifting, standing, sleeping, social, activities of daily living

31.  Psychological evaluation  Particularly in chronic pain  Up to 50% of chronic pain patients suffer from depression  Depression commonly undertreated or patients are non-compliant  Depression in pain patients is highly correlated with drug misuse, overdoses, and deaths

32.  Comorbidities should be considered  Renal and hepatic function: Can affect medication selection and dosing  Bowel function abnormalities  Other medications used by the patient  Affects selection of pain medication

33.  Home environment, social network, access to pharmacy, rehab services  Patient barriers – culture, co-morbid conditions, fears  Non-compliance  Too complicated a regimen  Adverse effects  Mental health problems-depression, drug abuse

34.  Identify a level that is acceptable to the patient so that they can deal with pain or have normal Activities of Daily Living (ADL)  Identify a level on the rating scale that requires re-evaluation by a professional  Conduct assessment of individuals with unacceptable pain ratings

35.  Prior Rx drug abuse and recreational drug use  Question to determine if behavior is  Addiction (see definition)  Brief experimentation  Trying to find effective pain relief (undertreated)  Addiction is rare in patients without prior abuse history  Inquire about legal problems in past related to drugs  Family history of drug or ethanol abuse – lose control of drug product

36.  State concern with patient early in treatment  See patient more frequently  Physical exams to detect indications of drug abuse  Track marks, inflamed nasal mucosa, tremor, tachycardia, etc.  Prescribe small quantities of medication more frequently  Urine toxicology screening

37.  See only one physician  Go to only one pharmacy  No early, night, or weekend refills  No unauthorized dose escalation  No giving medications to others

38.  Patient reports of pain and relief are to be considered valid  Listen to the patient and maintain dialogue with the family  Refer to Pain Management Specialists if unable to satisfy patient needs