浙江大学医学院：疼痛和镇痛药理学（PPT讲稿）Pharmacology for Pain and Analgesia

Pharmacology for Pain and analgesia Dept of Pharmacology Shi-Hong Zhang(张世红 shzhang713@zju.edu.cn SaperbPlanetcom

Pharmacology for Pain and Analgesia Dept of Pharmacology Shi-Hong Zhang (张世红) shzhang713@zju.edu.cn

What is pain An unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage. Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. It is unquestionably a sensation in a part of the body but it is also unpleasant and therefore also an emotional experience. Many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is no way to distinguish their experience from that due to tissue damage if we take this subjective report IASP Pain1979(6)249-252

What is pain An unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. It is unquestionably a sensation in a part of the body, but it is also unpleasant, and therefore also an emotional experience. Many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is no way to distinguish their experience from that due to tissue damage, if we take this subjective report…… IASP. Pain 1979(6)249-252

Physiology of Pain Pain sensation First pain: shal irp, pricking, well defined. As fibers Second pain: dull, aching, poorly localized, c fibers

Physiology of Pain Pain sensation First pain：sharp, pricking, well defined，A fibers Second pain：dull, aching, poorly localized, C fibers

Pain signals to brain stem and brain ightly myelinate As fibres Large cell (through secondary To supraspinal ain-projection targets neurons Heavily DRG myelinated Aβ fibres Dorsal Small cell bodies Unmyelinated Fibres neurons Ventral Ventral projection fibres Pain signals to spinal cord (through primary afferents Normal acute pain Milligan et al 2009

Milligan et al, 2009

Chronic pain Types and reasons Neuropathic pain Inflammatory pain Bone cancer pain Fibromyalgia igraine Psychogenic pain

Types and reasons Neuropathic pain Inflammatory pain Bone cancer pain Fibromyalgia Migraine Psychogenic pain Chronic Pain

How chronic pain can become a problem REDUCE ACTIVITY PHYSICAL DETERIORATION (eg. muscle wating oint stess) UNHELPFU BeeFs S THOUGHTS FEEUNGS OF CHRONIC DE EPRES SION LPLES SNESS EXCESSIVE PAIN REPEATED RRITABUTY SUFFERING TREATMENT SLEEP FAILURES DISTURBANCE LONGTERM USE OF SIDE EFFEC TS ANALGESIC (eg, stom Jch SEDATNE DRUGS problems leth angy. constip ation LOSS OF JOB F|NAc风AL DIFFICULTIES. FAMILY Copyright: M K Nicholas PhD STRESS Pain management Research Insttute Royal North Shore Hospital st Leonards Nsw 2005 Australla

Chronic pain Mechanisms Peripheral input Central sensitization

Mechanisms： Peripheral input Central sensitization Chronic Pain

Table Neuronal mediators and receptors involved in central sensitization 1-1e Neurotransmitter/mediator Target receptors Outcome Glutamate AMPA and nmDa Opening of receptor channels Neuropeptid Substance P NK-1 Enhanced glutamatergic synaptic transmission NKA NK-2 CGRP CGRP Prostaglandin E2 EP(pre-and postsynaptic Enhanced nociceptor sensitivity Pro-inflammatory cytokines IL-1B Type 1IL-1 COX-2 upregulation TNF-a TNF types 1&2 Sensitization of nociceptive neurons Second messenger systems Nitric oxide Sensitization of spinothalamic tract cells AMPA, a-amino-3-hydroxy-5-methyl-isoxazole-4-propionic aad; NMDA, N-methyl-D-aspartate: CGRP, calcitonin gene-related peptide, NK, neurokinin; EP, prostanoid receptors, IL-1B, interleukin-1B: TNF-a, tumour necrosis factor-a COX-2, cydooxygenase-2 Plus dysfunction in inhibitory systems including opioids cannabinoids, norepinephrine adenosine

Plus dysfunction in inhibitory systems, including opioids, cannabinoids, norepinephrine, adenosine…

Analgesics(pain killer) NSAIDs and other anti-inflammatory drugs Opiates and morphinomimetic Some tricyclic antidepressants Some antiepileptic drugs ocal anesthetics a Others ketamine mexiletine, etc

Analgesics (pain killer) ◼ NSAIDs and other anti-inflammatory drugs ◼ Opiates and morphinomimetics ◼ Some tricyclic antidepressants ◼ Some antiepileptic drugs ◼ Local anesthetics ◼ Others: ketamine, mexiletine, etc

3 Antipyretic analgesic) and %h i Antettmmato (Non-sterofdalanti-inflammatory drugs, NSAIDs)

Antipyretic, Analgesic, and Anti-inflammatory Drugs (Non-steroidal anti-inflammatory drugs, NSAIDs)