Pain Physiology SLS
Transcription
Pain Physiology SLS
Pain Physiology in the Chronic Pelvic Pain Context Juan Diego Villegas-Echeverri, MD, FACOG Unidad de Laparoscopia Ginecológica Avanzada y Dolor Pélvico ALGIA Clínica Comfamiliar Pereira, Colombia SA [email protected] Pain Physiology in the Chronic Pelvic Pain Context Juan Diego Villegas-Echeverri, MD, FACOG No relevant financial relationships in the past twelve months by presenter or spouse/partner. Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It is a complex collection of multiple, learned perceptions that change over time and that motivate individuals to circumstance appropriate self-protective action. . IASP Task Force on Taxonomy. Pain Terms. A Current List with Definitions and Notes on Usage. In: Classification of Chronic Pain. Part III. Merskey H, Bogduk N. IASP Press, Seattle, 1994. . International association for the study of pain IASP. Annual meeting. Seattle, 2000 . Berkley KJ. Neuroscience, FSU. 2005 Chronic Pelvic Pain • • • • Non-malignant Non cyclic pain* >3mo duration* Localizes – – – – Anatomic pelvis Anterior abdominal wall at or below the umbilicus Lumbosacral back Buttocks • Sufficient severity to cause functional disability or lead to medical care. • Related negative cognitive, behavioral and social consequences. . Howard F: ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists. ACOG Number 51, March 2004 . Fall M, Baranowski AP, Fowler CJ et al. EAU guidelines on chronic pelvic pain. Eur Urol 2004;46:681–9. A lack of physical findings does not negate the significance of a patient’s pain. Normal examination results do not preclude the possibility of finding pelvic pathology. It is more likely that patients are poorly evaluated and not that the physical examination is normal. . Howard F: ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists. ACOG Number 51, March 2004 Chronic Pelvic Pain Syndrome • • • • CPP Impaired usual function Signs of depression Pain out of proportion to pathology • Unresponsive to usual therapy • Altered family roles . ACOG Patients educational pamphlet AP 129. Chronic pelvic pain. Washington DC 1989 . Issa W, Roumeguere Te, Bossche MV. Chronic pelvic pain syndrome. Rev Med Brux. 2013;34(1):29 Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions • • • • 20 - 30% of all ObGyn Office visits 15 - 20% of all ER ObGyn Visits 20 - 40% of all Gyn Laparoscopies Up to 61% undiagnosed - untreated • 41% never seek consultations • 31% with symptom related anxiety (compared with 7% without CPP) • 50% had also urinary symptoms and/or functional bowel disease . Zondervan KT, Yudkin Pl et al. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Brit J Gen Practice 2001;541 . Zondervan KT, Yudkin Pl et al. Chronic pelvic pain in the community. Symptoms, investigations and diagnoses. Am J Obstet Gynecol 2001;184:1149 • Up to 75% of Gyn medical disability in the United States • 80% of patient’s are unsatisfactorily managed • Only 15% of physicians surveyed said they “enjoyed” caring for CPP patients . Zondervan KT, Yudkin Pl et al. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Brit J Gen Practice 2001;541 . Zondervan KT, Yudkin Pl et al. Chronic pelvic pain in the community. Symptoms, investigations and diagnoses. Am J Obstet Gynecol 2001;184:1149 . Pizzo PA, Clark NM. Alleviating suffering 101--pain relief in the United States. N Engl J Med 2012;366(3):197 Quality of Life • • • • • • • • • Inability to exercise Difficulty sleeping Lack of enjoyment of leisure Inability to perform chores Interference with socializing Difficulty walking Interference with sexuality Difficulty concentrating Inability to work 81% 79% 67% 65% 65% 59% 54% 49% 41% . Mathias SD et al. Obstet Gynecol. 1996;87:321-327. . Postgraduate course 5. Chronic Pelvic Pain. IPPS. 31st AAGL meeting.November 2002. Miami, Fla . Yunker A, Sathe NA, Reynolds WS, Likis FE, Andrews J. Systematic review of therapies for noncyclic chronic pelvic pain in women. Obstet Gynecol Surv 2012;67(7):417 Cost • Medical cost U$ 1.2 billion/year • Productivity loss U$ 15 billion/year . Association of professors of gynecology and Obstetrics: monography January 2000 Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions Pain Source Nociceptive Somatic Pain Non nociceptive Visceral Pain Neuropathic Pain Mixed Pain Acute Pain Chronic Pain Pain Duration . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 Nociceptive pain arises from the stimulation of specific pain receptors . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 Somatic Pain – Caused by the activation of pain receptors • Body surface • Musculoskeletal tissues – Usually aggravated by activity and relieved by rest – Receptors respond to stimuli released from damaged cells • • • • • Heat Cold Vibration Stretch Chemical . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 Visceral Pain – Caused by damaged or injured internal organs or abdominal muscles (spasm) – Caused by the activation of pain receptors in the chest, abdomen or pelvic areas – Vague and not well localized – Usually described as pressure-like, deep squeezing, dull or diffuse – Referred pain . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 ..Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 Non Nociceptive Pain arises from within the peripheral and central nervous system . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 Neuropathic Pain • Caused by injury or malfunction to the spinal cord and peripheral nerves • Typically a burning, tingling, shooting, stinging, or "pins and needles" sensation • Also complain of a stabbing, piercing, cutting, and drilling pain • Usually occurs days, weeks or months after the injury • Tends to occur in waves of frequency and intensity • Is diffuse and occurs at the level or below the level of injury . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 . Attal N. Neuropathic pain: mechanisms, therapeutic approach, and interpretation of clinical trials. Continuum (Minneap Minn) 2012 (1):161-75 Acute Pain • Typically is produced by sudden injury • Accompanied by physical signs • Tends to resolve as the injury or disease does . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 . Inui K. Pain pathway. Brain Nerve. 2012 ;64(11):1215 Chronic Pain • • • • 3-6 mo duration Persistent pain In many cases no physical cause can be found Is a disorder in itself rather than being the symptom of a disease process • Repeated pain from an acute injury changes the nervous system responses . Wall and Melzack's Textbook of Pain. Churchill Livingstone; 5th edition 2005 . Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012 ;13(10):936 . Fornasari D . Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012 ;32 Suppl 1:45 . Inui K. Pain pathway. Brain Nerve. 2012 ;64(11):1215 . Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197 Acute vs. Chronic Pain • Acute Pain Symptom of tissue damage and an underlying disease • Chronic Pain Pain becomes a disease «Some individuals who have acute pain can be caught in a vicious cycle that leads to chronic pain and disability» . Crombez G, Eccleston C, Van Damme et al. Fear-avoidance model of chronic pain: the next generation. Clin J Pain. 201228(6):475 . Quinlan J, Carter K. Acute pain management in patients with persistent pain. Curr Opin Support Palliat Care 2012; 6(2):188 Pain is a direct or indirect consequence of several diseases. However patients with moderate to severe pain are often under-treated in both developing and developed countries(…) It is important to recognize that pain is a problem in its own right, not “just” an indicator of an underlying disease or damage process, but one which extracts a great toll on individuals and society. Alleviation of pain itself, as a symptom, should be a therapeutic target. In order to improve the quality of life, the objective should be to avoid any unpleasant perception with an approach based on the right communication between the care giver and the patient WHO Normative Guidelines on Pain Management. Report of a Delphi Study to determine the need for guidelines and to identify the number and topics of guidelines that should be developed by WHO Geneva, June 2007 Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions Descartes “Tubules” • 3 components – First order neurone • cell body in dorsal root ganglion • Transmits pain from a peripheral receptor – Second-order neurone • Dorsal horn of the spinal cord • Axon crosses the midline • Ascend in the spinothalamic tract to the thalamus – Third-order neurone • Projects to the postcentral gyrus (via the internal capsule) • Generate periferical response . Fornasari D. Pain mechanisms in patients with chronic pain.Clin Drug Investig 2012;32 Suppl 1:45 • The progression of pain research has been hindered by the dominating view that pain is a purely nociceptive phenomenon • Now we know is much more complex (even more for the chronic pain) – Peripheral receptors – Neural pathways – Spinal Cord mechanisms & long tracts – Brainstem, thalamus, cortex & other areas – Descending pathways . Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155 . Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197 A beta fibres Local interconnections Initial connections Ascending pathways A delta fibres Spinal cord Gate Control Neospinothalamic tract Perception of Pain In cerebral cortex First pain Second pain (pain only nociceptors) (polimodal nociceptors) A delta fibres Spino-reticulo-diencephalic pathway C fibres Peripheral receptors Sensory and motor cortex areas Premotor cortex Pre Frontal cortex Other parts of the parietal cortex Cingulate cortex Insula Occipital cortex Descending modulation Brain regions involved in pain processing Somatosensory Cortex Prefrontal Cortex Insular Cortex Thalamus Anterior Cingulate Cortex (ACC) / Locus coeruleus Anatomy of Pain Overlaps Anatomy of Emotion . Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9(4):463 Common areas of activation in pain studies (PET and MRI ) • Anterior Cingulate Cortex (ACC) / Locus coeruleus – Cognitive functions and reasoning • • • • Reward Anticipation Decision Making Empathy Emotion – • • • • Integrates emotional stimuli with attentional functions Prefrontal cortex – Perform and accomplish – Working memory – Decision making – Planning and judgment Insular Cortex – Processes convergent information to produce emotionally relevant context for sensory experience Somatosensory Cortex Thalamus (and Amygdala) • Processing • Memory of emotional reactions . Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005;9(4):463 Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusions • Pain mechanisms in patients with chronic pain – Altered Pain processing – Cross – Talk – Convergence and Hiperalgesia • Visceral – somatic • Visceral - visceral – Dorsal horn neuroplasticity – Centralization – Neurogenic inflamation / Antidromic transmission – Visceral “Silent” Afferents .Fornasari D. Pain mechanisms in patients with chronic pain. Clin Drug Investig 2012;32 Suppl 1:45 Altered Pain-Processing Severe, unrelieved pain for more than 24 hr Excessive and prolonged stimulation of N-methyl-Daspartate (NMDA) receptors Plastic neuropathic change at dorsal horn receptor cell Produces hyperexcitable neurons, allodynia and hyperalgesia . Doggweiler-Wiygul R. Chronic pelvic pain. World J Urol 2001;19:155 . Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13(10):936 Repeat Stimulation of Nociceptive Neurons Changes Nerve Fibers Lowers Threshold Peripheral Sensitization Exaggerated Transmission Response Recruits higher and Lower Neurons Self-Sustaining Activation . Doggweiler-Wiygul R. Chronic pelvic pain. World J Urol 2001;19:155 . Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13(10):936 Spinal Windup Neuronal plasticity Barrage of painful stimuli to dorsal horn Decrease threshold or loss of inhibition (allodynia) Expansion of receptive fields Permanent biochemical change Exaggerated reflex output with end-organ dysfunction Up regulation of sensory processing . Puretić MB, Demarin V. Neuroplasticity mechanisms in the pathophysiology of chronic pain. Acta Clin Croat 2012;51(3):425 . Herrero JF, Laird JM, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000 ;61(2):169 Zermann D et al. J Urol. 1999;160:102-105. Cross-talk The very strong electrical signals originated in poorly isolated (or poorly myelinated) nerves produce de novo electrical signals on adjacent afferent nerve fibers that are not involved in the painful stimuli . Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: implication for the pathogenesis of interstitial cystitis/bladder pain syndrome. Int J Urol 2012;19(5):429 . Ren K, Dubner R. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008;21(5):570 Visceral somatic convergence • Only 2 to 7% of all afferent fibers of each dorsal root ganglion are visceral • The interneurons in the dorsal horn are greatly influenced by somatic fibers • So – The somatic pain is referred as visceral pain (specially in the abdominal wall) – The visceral pain is diffuse and poorly located • Visceral muscular reflex and induced myalgia - PFTM . Giamberardino MA, Berkley KJ, Affaitati G, et al. Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain 2002;95:247-57. . Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155 Visceral-somatic hiperalgesia Refered neurogenic inflamation – BPS/IC + vulvodinia – IBS + abdominal trigger points . Staud R. Peripheral pain mechanisms in chronic widespread pain. Best Pract Res Clin Rheumatol 2011;25(2):155 . Brumovsky PR, Gebhart GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci 2010;153(1-2):106 Visceral - visceral hiperalgesia – BPS/IC + IBS – Endometriosis + BPS/IC (”evil twins”) – Hernias + PCS . Chung MK, Chung RP, Gordon D. Interstitial cystitis and endometriosis in patients with chronic pelvic pain: The "Evil Twins" syndrome. JSLS 2005;9(1):25. . Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: implication for the pathogenesis of interstitial cystitis/bladder pain syndrome. Int J Urol 2012;19(5):429 Dorsal horn neuroplasticity • Nociceptive stimuli modulation in patients with CPP (highly subjective) – Primary hiperalgesia • Afferent pathways remodeling - dorsal horn • Downstream influences from supraspinal sites – Secondary hiperalgesia and allodynia • Hiperalgesia far from the original painful site . Crosby ND, Weisshaar CL, Winkelstein BA.Spinal neuronal plasticity. Neurosci Lett 2013. doi:pii: S0304-3940(13)00224 . Wu J, Hu Q, Huang D, Chen X, Chen J. Effect of electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn. Brain Res 2012;1448:11-9 Central sensitization • Enhanced nociceptive synaptic transmission within the spinal cord following persistent pain states – – – – Dissociation of pain Perception from a noxious stimulus or injury Expansion of hyperalgesia beyond the site of injury Extra-dermatomal hypersensitivity across other somatic and visceral structures . Farmera MA, Baliki MN. A dynamic network perspective of chronic pain. Neuroscience Letters 2012; 520:197 • • • • • • Despite removal of original (primary pain generator) “insult” pain persists (30-50%) The dorsal horn is still hyper excitable with spontaneous activity. Phantom limb Spinal memory Reorganization of somatosensory cortex “ A chance to cut is NOT a chance to cure” . Gustin SM, Peck CC, Cheney LB, Macey PM, Murray GM, Henderson LA. Pain and plasticity: is chronic pain always associated with somatosensory cortex activity and reorganization? J Neurosci 2012;32(43):14874 . Garland EL. Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care 2012;39(3):561 . Saab CY. Pain-related changes in the brain: diagnostic and therapeutic potentials. Trends Neurosci 2012;35(10):629 Neuro-inflammation by antidromic transmission • Release of neuropeptides at the terminus of afferent nerves – – – – Substance P CRGP Neurokinin A Neurokinin B • Resulting in tissue reaction – Reddening (vasodilation) – Edema (plasma extravasation) – Hyperalgesia • Non neuropathic refered pain – Dyspareunia and PCS . Wesselmann U. Neurogenic inflammation and chronic pelvic pain. World J Urol 2001;19:180 . Hornick L, Slocumb JC. Treating chronic pelvic pain. Focus on pain triggers and neurogenic inflammation. Adv Nurse Pract 2008;16(2):44 Visceral “Silent” Afferents • Thinly or unmyelinated – easily damaged locally • 30% to 80% visceral afferents are silent • Silent afferents become active with prolonged stimuli • Silent afferents sensitization play major role in tissue • Many more interneuronal synapses . Keszthelyi D, Troost FJ, Simrén M, Ludidi S, Kruimel JW, Conchillo JM, Masclee AA. Revisiting concepts of visceral nociception in irritable bowel syndrome. Eur J Pain 2012;16(10):1444 . Bueno L, Fioramonti J. Visceral perception: inflammatory and non-inflammatory mediators. Gut 2002;51 Suppl 1:i19 . Schott GD. Visceral afferents: their contribution to 'sympathetic dependent' pain. Brain 1994;117 ( Pt 2):397 Presentation Outline 1. 2. 3. 4. 5. 6. Definitions Why bother? Scope of the problem Types of pain Pain pathways The neuro pathologic response to pain Conclusion In summary • Pain itself can be the disease • Sometimes the normal responses to pain create new pain generators – Look for the original insult – if still present – Treat all sources of pain and dysfunction – “Turn down the pain” • Avoid inducing further wind-up in patients with pre-existing upregulation If you only have a hammer, it’s tempting to treat everything as if it were a nail. - Abraham Maslow (1.908 – 1.970)