General Definitions of Pain Term sometimes given to strictly mental processes.

1. General Definitions of Pain Term sometimes given to strictly mental processes. Animals’ aversive reaction to strong stimulation Physical damage to the body, i.e. burn or cut. Previous injury - could be described as painful, unbareble

2. Pain and Pleasure: • Intensive Theory: Weber vs Erb and Goldscheider • Pattern Theory. Nafe (1929) • Muller’s Theory of Specific Nerve Energies: Von Frey proposed four distinct sets of somatic sensory receptors: touch, warm, cold and pain.

3. Aberrant pain • Inflammation and hyperalgesia • primary hyperalgesia • secondary hyperalgesia - allodynia where a previously non-noxious stimulus induces pain • Referred Pain • Pain and Pathology

6. In man stimulation of the afferents conducting at > 40 m/sec • produce the sensation of touch, while < 25 m/sec (Ad) fibers • indicate pain, increase intensity of stimulation and include ‘C’ • fibers then subjects report intense pain. • Idea of two pains: First pain (pricking) which is associated • with Ad fibers and Second pain (burning and diffuse) associated • with ‘C’ fibers. • The Ad fibres can be mechanosensitive only or mechano-heat • sensitive.

7. Pressure block. Large fibers are blocked first, small last. • Touch sensation is lost first and pain last. • Local Anaesthetic. Small fibers are blocked first and large • last. Here pain is lost first and touch last.

11. The polymodal fibers in monkey respond to heat at temperatures • greater than 45 deg C also to mechanical stimulation and to noxious chemical stimulation. One of the most used substances to produce chemical pain is capsaicin, the active substance in chilli.

12. “Silent” - initially silent nociceptors. These are reported in • muscle, joints and visceral tissues and most recently in the • skin responding to sustained pressure on the skin. ‘C’ fibers • that are initially unresponsive become responsive to • stimulation. What is significant about these observations is • that the ‘C’ fibers that do respond initially give an initial • response and then adapt after time. But the “initially silent” • fibers don’t respond to start with and then they respond after • about --- (30 min ) with a constant response. The important • psychophysical observation is that subjects don’t initially • report pain but then after period they report pain.

13. The polymodal fibers in monkey respond to heat at temperatures • greater than 45 deg C but on repeated application there can be • a lowering of threshold and an increase in activity with repeated • stimulation. • This can be mimicked by formalin injection as a model • for primary hyperalgesia. Sensitization has two components. - • peripheral (local to the nerve endings ) and central. There is some • evidence that NGF is “pivotal” in both aspects. The NGF depletes • the mast cells which release histamine and 5-HT.

21. Central pathways • How does touch information get to the CNS? • How does pain information get to the CNS?

23. Central Sensitization might be due to the transport of NFG to the CNS where it acts to produce increased sensitivity. The central effect is likely to be mediated by EAA’s l-glutamate or l-asparate and and is blocked by NMDA antagonists. One hypothesis is that it is the accumulation of intracellular Ca++ that mediates increases in NO, arachodonic acid and PKC. The hypothesis (unspecified) is that these intracellular messengers produce long-term alterations in the membrane properties leading to increased excitability.

24. General Definitions of Pain Term sometimes given to strictly mental processes. Animals’ aversive reaction to strong stimulation Physical damage to the body, i.e. burn or cut. Previous injury - could be described as painful, unbareble

25. McGill Pain Questionnaire: • Sensory-discriminative quality (throbbing, gnawing, • shooting …) • 2. Motivational-affective (tiring, sickening, fearful … ) • 3. Cognitive evaluative quality (no pain, ,mild, intense, • excruciating … )

28. cingulate and insula cortex

29. Mild discomfort of 47 deg water verses more discomfort: Illusory pain from alternating warm and cool bars – activates Cingulate. cingulate and insula cortex

32. Descending pain modulation • Naturally occurring opiates • endorphin • enkephalins

36. Placebo effect