1. Pain, physiology and
pharmacology
Lasse Ståhle
150925

2. What is pain?
IASP* definition: An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Swe: En obehaglig sensorisk och emotionell upplevelse som är knuten till verklig eller potentiell vävnadsskada, eller beskriven i termer av en sådan skada.
Thus, pain is always something experienced by the subject and there is no such thing as objective pain. Importantly, a given stimulus will not result in the same pain in different subjects and neither on two different occasions in the same subject. Nevertheless, patient history and clinical examination can help put the patient in the perspective of the patient population in general, facilitating diagnosis and choice of treatment.
*International Association for the Study of Pain

3. Nociceptive pain stimuli

5. Sodium channel NaV1.7 in nociceptive primary afferents

6. Hereditary pain conditions and pain sensitivity due to NaV1
Hereditary pain conditions and pain sensitivity due to NaV1.7 genetic variation

7. Fast inactivation of NaV1.7 is slower in mutated channel
Paroxysmal extreme pain disorder (previously familial rectal pain syndrome).
Fertleman, C; Ferrie, C; Aicardi, J; Bednarek, N; Eeg-Olofsson, O; Elmslie, F; Griesemer, D; Goutieres, F; Kirkpatrick, M; Malmros, I; Pollitzer, M; Rossiter, M; Roulet-Perez, E; Schubert, R; Smith, V; Testard, H; Wong, V; Stephenson, J
Neurology. 69(6): , August 7, 2007.
DOI: /01.wnl f
Figure 2 Clinical features of attacks in paroxysmal extreme pain disorder (PEPD)(Top left two images) Flushing of lower half of body following a rectal attack in a baby (IV:1, Family 4). (Bottom left) Harlequin color change affecting the face (II:2, Family 9). (Top right) Cartoons of the various harlequin color changes observed in one infant with PEPD (II:2, Family 9). (Bottom right two images) Attack of jaw pain provoked by eating (II:2, Family 9).
Fast inactivation of NaV1.7 is slower in mutated channel
©2007 American Academy of Neurology. Published by LWW_American Academy of Neurology. 2

8. Opening of NaV 1.7 at smaller changes in transmembrane voltage
Erythromelalgia
Opening of NaV 1.7 at smaller changes in transmembrane voltage

9. Clinical significance of NaV1.7 polymorphism R1150W
Allellic frequency for A-mutation is 10%, i e 1% homozygous mutated, 81% homozygous
”wild-type” and 18% heterozygous.

10. Ascending pain pathways and target regions

11. M Ploner, H.-J Freund, A Schnitzler
Fig. 1. Transaxial MRI-slices at 42 mm (left) and 18 mm (right) parallel above the anterior commissure-posterior commissure-line. Scales give coordinates in mm according to the Talairach frame of reference (Talairach and Tournoux, 1988). Markers (*) indicate t...
M Ploner, H.-J Freund, A Schnitzler
Pain affect without pain sensation in a patient with a postcentral lesion
Pain, Volume 81, Issues 1–2, 1999, 211–214

13. Fig. 2
Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain-an fMRI analysis.
Valet, Michael; Sprenger, Till; Boecker, Henning; Willoch, Frode; Rummeny, Ernst; Conrad, Bastian; Erhard, Peter; Tolle, Thomas
Pain. 109(3): , June 2004.
DOI: /j.pain
Fig. 2 . Cerebral pain processing (A) without attentional distraction and (B) during attentional distraction. The images represent pain-specific activation effects (P<0.05 corr.) that are corrected for temperature related activation effects. Without distraction noxious stimulation (A) evokes activation of the sensory-discriminative pain coding system (e.g.: S1, S2, lateral thalamus, posterior insular cortex) and affective-motivational system (medial thalamus, ACC, anterior insular cortex). During distraction (B) induced by the Stroop-task the same noxious stimulation is no longer able to activate the former pain network. Activation maps are superimposed on the mean normalized anatomical T1 images of the subjects. Radiological convention: Right side of the image corresponds to left side of the brain.
© 2004 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

15. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects
 Average normalized mechanical pain tolerance score under conditions of slow wave sleep (SWS) and rapid eye movement (REM) sleep interruption. Pain tolerance was assessed at baseline day (D2), after total sleep deprivation (D3), selective sleep interruption (D4, D5) and sleep recovery (D6). All values are ratios in which the mean pain tolerance score at the indicated measurement is the numerator and the mean pain tolerance score at D2 (baseline) is the denominator. SWS recovery produced a significant enhancement of pain tolerance (D2 versus D6, P=0.04). The differences between periods were not statistically significant.
© IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.
Journal of Sleep Research Volume 10, Issue 1, pages 35-42, 7 JUL 2008 DOI: /j x

16. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects
 Correlation between slow wave sleep (SWS) amount and average normalized mechanical pain tolerance score after SWS interruption (▮ D4, ◆ D5) and recovery (▴ D6) days. Sleep amount and pain were compared in healthy subjects (n=9) by using a correlation test (r=0.53; P=0.003).
© IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSION' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.
Journal of Sleep Research Volume 10, Issue 1, pages 35-42, 7 JUL 2008 DOI: /j x

21. Brain mechanisms of pain affect and pain modulation
Fig. 2. Endogenous activation of the μ-opioid system associated with the sensory and affective dimensions of pain perception. Changes in μ-opioid receptor availability were evaluated using the radioligand [11C]carfentanil and PET to assess the endogenous activ...
Pierre Rainville
Brain mechanisms of pain affect and pain modulation
Current Opinion in Neurobiology, Volume 12, Issue 2, 2002, 195–204

22. Definitions
Nociceptive pain Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors. Neuropathic pain Pain caused by a lesion or disease of the somatosensory nervous system. Nociplastic pain Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptor or evidence for disease or lesion of the somatosensory system causing pain Pain of unknown origin

23. Pain subtypes
Nociceptive
Neuropathic
Nociplastic

24. Referred pain

25. Peripheral sensitization
Lasse Ståhle

26. Allodynia, hyperalgesia, dysesthesia, hypoesthesia, anesthesia

27. Lasse Ståhle

28. Trauma

29. Arthritis - gout

30. Osteoarthrosis/ osteoarthritis