PHARMACY 312 MSK Lecture 2 Pathophysiology of Pain 2024.pdf

Bachelor of Pharmacy Monday, 9th September 2024 PHARMACY 312 Pathophysiology of Pain Dr Audrys G. Pauza Department of Physiology School of Pharmacy Disclosure No disclosure. 2 Session learning outcomes By the end of the session you will: Describe the process of tra...

Bachelor of Pharmacy Monday, 9th September 2024 PHARMACY 312 Pathophysiology of Pain Dr Audrys G. Pauza Department of Physiology School of Pharmacy Disclosure No disclosure. 2 Session learning outcomes By the end of the session you will: Describe the process of transduction and transmission of nociceptive stimuli Describe modulation of nociceptive signals Contrast nociceptive and neuropathic pain 3 What is pain? “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” International Association for the Study of Pain Pain is also a protective mechanism, and an essential learning tool Pain is a powerful emotion 4 What is pain? Cont. From biological point of view, pain is a product of brain function Sensation and Perception 5 Types of Pain 1. Nociceptive (Acute) Pain ‘Physiologic pain’ Protective Alerts body to a problem Protects from further injury Aids healing (forcing body to rest) 2. Neuropathic Pain Pathophysiologic Harmful 6 Nociceptive Pain Nociception: The process of encoding noxious stimuli to neural signals Noxious Stimuli: Thermal (high or low temperatures) Mechanical (e.g. pinching) Chemical (e.g. irritants, acid) 7 Nociceptive Pain Nociception: The process of encoding noxious stimuli to neural signals Four steps: 1. Transduction 2. Transmission 3. Perception (briefly covered today) 4. Modulation 8 Historical context Descartes, 1664 9  Modern context Perception ! Transmission 2 Modulation 3 Nociception, Pain, Negative Moods, and Behavior Selection Transduction Neuron, 87:3 pp474-491 1 10 Transduction cont. Transduction: Converting one form of energy to nerve signals Action potential Transduction Stimuli: Temperature Mechanical Chemical Nerve fibre Free nerve 11 ending  Transduction cont. Stimulus Stimuli are sensed by specialised proteins called receptors Receptor Detection of a stimulus leads to changes in the receptor Increase in ion flow across the membrane instigates an Action action potential potential Receptors are important drug targets 12 Fit for Purpose Different types of receptors Extracellular Shear force ΔVm G⍺ Ligand Voltage Mechanically G-protein -gated -gated -gated coupled receptors Ion channels Intracellular 13 Transduction cont. Touch, pressure, vibration, skin stretch Nociceptors Neuroscience. 2nd edition. Purves D, Augustine GJ, Fitzpatrick D, et al., 14 editors. Sunderland (MA): Sinauer Associates; 2001. Transduction cont. x = 1 mm y= 0.83 mm z= 0.11 mm Nerve endings in the epidermis Kim, D.H., Lee, S.J., Kim, J.H. et al. Whole structural reconstruction and quantification of epidermal innervation through the suction blister method and skin-clearing technique. Sci Rep 12, 13596 (2022). 15 Transduction cont. Nociceptors Free nerve endings Located in somatic and visceral structures Not all organs have nociceptive innervation! Respond to varying stimuli temperature, mechanical, chemical Receptors (e.g. TRPV1 = heat >42 ºC) TRPM8 = cold