Physiology of Pain Lecture (Dr. Karius) TEST 3

Question 1

Pain: The Introduction

Answer 1

Pain is DIFFERENT from all Other Senses because:
1) The Sensation is ELICITED by MULTIPLE STIMULI

2) It “PRE-EMPTS) all OTHER SIGNALS
3) These differences result in MULTIPLE ALTERATIONS in the Physiological Functioning of the Pain Pathways

Pain can also be CHARACTERIZED as:

1) FAST PAIN
- Generally associated with the Immediate Injury (Sharp Pain)

2) SLOW PAIN:
- Often Characterized as DULL or ACHY
- Often occurs AFTER the Injury

Pain can be CHARACTERIZED by LOCATION:

1) Deep Pain
2) Muscle Pain
3) Visceral Pain
4) Somatic/ Cutaneous Pain
* **The Characteristics of these forms of Pain VARY due to Physiological and Anatomical Considerations

Question 2

Sensory Receptors: General Information

Answer 2

• Many are BARE NERVE ENDINGS with Specialized Ion Channels that OPEN in response to SPECIFIC STIMULI (Ex Thermoreceptors)
• Some Sensory Receptors show QUITE EXTENSIVE Morphological Specialization

Question 3

Review of Nociceptive System

Answer 3

Sensing NOXIOUS Stimuli: The Nociceptors

• Bare Nerve Endings
• Two Types of Fibers:
  1) A GAMMA FIBERS: Small, Sparsely MYELINATED. Fast, SHARP PAIN

2) C FIBERS: UNMYELINATED Fibers associated with DULL PAIN (SLOW PAIN)

Question 4

Sensing Noxious Stimuli: The Nociceptors

Answer 4

ISSUE:
- Must be able to Detect a Wide Variety of Damaging Stimuli

TYPE of NOCICEPTORS:
1) Sensitive to BOTH THERMAL and MECHANICAL Stimuli (Majority)

2) Sensitive ONLY to THERMAL Stimuli
3) Sensitive ONLY to MECHANICAL
4) SILENT/ SLEEPING

Many Mixed Modality Nociceptors also express a MECHXNOSENSITIVE Na+ Channel (SCN9A or Na1.7)
- Mutations in this Channel lead to an ABSENCE of PAIN SENSATION!!!!!!!!!!!!!

• Another Class of MUTATION produces a PAROXYSMAL PAIN SYNDROME!!!!!

Question 5

Sensing Noxious Stimuli: The Nociceptors

Description

Answer 5

1) Unlike other receptors, NOCICEPTORS Express a Number of LIGAND-GATED Receptors (In Addition to the Stimulus- Gated Channels) which ALTER the Sensitivity of the NOCICEPTORS to Input

2) These Include Receptors for:
a) Substance P
b) The KININS (Ex Bradykinin)
c) ATP
d) H+

2a) Interestingly, this Collection of Chemicals also EXISTS in the Spinal Cord, where they also Influence NOCICEPTIVE Inputs at those Synapses!!!
2b) When these Chemicals bind to their Receptors, they Change the SENSITIVITY of the Nociceptors (Usually Increasing) and Activate the SILENT NOCICEPTORS!!!!!
2c) Activated Nociceptors, the DAMAGED TISSUE, and Recruited WBC RELEASE THESE INTO THE PERIPHERY AS WELL AS IN THE SPINAL CORD!!!!!

Question 6

Sensing Noxious Stimuli: Pathways to the Brain

Answer 6

There are Multiple Pathways to the Brain:
1) Dorsal Columns: PROPRIOCEPTIVE and Discriminative (FINE TOUCH)

2) Spinothalamic Tract: FAST PAIN
3) Spinoreticulothalamic System: SLOW PAIN
4) Spinocerebellar Tract

Question 7

Sensing Noxious Stimuli: The Spinal Cord

Answer 7

A) Neurotransmitter Released:

1) EAA (From A Delta): Acting Primarily on Non-NMDA Receptors
* FAST PAIN*

2) From C Fibers:
- Substance P
- EAA

*** B) Nocicpetors that travel with the SPINORETICULOTHALAMIC Pathway (Slow Pain) Synapse on an INTERNEURON in the Spinal Cord before CROSSING and ASCENDING to the RETICULAR FORMATION

C) This Synapse is the Site of Much MODULATION of Spinal Cord Function:

• Local (GATE THEORY)
• Descending (OPIOD PATHWAYS)

Question 8

Sensing Noxious Stimuli: Visceral Pain

Answer 8

• The Visceral AFFERENT travel with AUTONOMIC NERVES rather than with either of the Two Spinal Pathways described already

Question 9

Central Processing of Noxious Stimuli: The Brain

Introduction

Answer 9

• Unlike other senses, NOCICEPTIVE INPUT is DISTRIBUTED WIDELY in the Cortex!!!!
• S1 and S2 receive INPPUT from the NOCICEPTORS and play a role in LOCALIZING the PAIN!!!

Question 10

Central Processing of Noxious Stimuli: The Brain

INSULAR CORTEX

Answer 10

The INSULAR CORTEX is particularly important in the INTERPRETATION of NOCICEPTIVE INPUTS:
1) Processes Information about the INTERNAL STATE of the Body

2) Contributes to the AUTONOMIC RESPONSE to the Pain
3) INTEGRATES AL SIGNALS RELATED TO THE PAIN (Asymbolia)!!!!!!!!!!!!!!!!!!

Question 11

Central Processing of Noxious Stimuli: the Brian

Description

Answer 11

• Lesions in any one are DOES NOT ABOLISH the ability to Experience Pain, although the Experience is CHANGED
• Many Nociceptive Inputs go to the AMYGDALA. This is particularly important for activating/ producing the Emotional Components inherent in the SENSATION of Pain

Question 12

Central Processing of Noxious Stimuli: Visceral Pain

Answer 12

• Visceral Nociceptors, traveling with the Autonomic Nerves, have additional Synapses WITHIN the HYPOTHALAMUS and the MEDULLA
• These additional Synapses form the basis of the Physiological Changes associated with VISCERAL PAIN, including DIAPHORESIS and ALTERED Blood Pressure

Question 13

The Gate Theory of Pain

Answer 13

• Based in part on the Observation that other SOMATIC INPUT can alleviate Pain (Rubbing the Area)

* The First Synapse onto Interneuron: Is the site where the Substance P and EAA are being released because it is a C Fiber!!!**

STEP 1:
- Activate A Beta Fibers (Bright Green) by the Normal Stimuli. The A Beta Fiber has a Branch the travels via the DORSAL COLUMNS, BUT it also Branches WITHIN the Spinal Cord

STEP 2:
- The A Beta Fiber (Green) releases EAA and ACTIVATES an INHIBITORY INTERNEURON (Yellow) in the Spinal Cord

STEP 3:
- The INHIBITORY Interneuron releases GLYCINE to INHIBIT the activity of the SECOND ORDER NEURON in the Pain Pathway

END RESULT:
- Rubbing the area of Skin ACTIVATED the A Beta Fiber will REDUCE the Sensation of Pain!!!!!!

Question 14

Descending Mechanisms of Painful Inputs

Answer 14

Basic Idea: Use Presynaptic INHIBITION to reduce Activation of the Second-order Nociceptive Neuron in the SPINAL CORD

STEP 1:
- Neurons in the PERIAQUEDUCTAL GRAY are activated by Numerous Inputs, Including OPIATE (Mu Receptors), EAA, and CANNIBINOIDS (CB1 Receptor)

STEP 2:
- Axons from the PAG Neurons travels to the MIDLINE RAPHE NUCLEI (Serotonin) and release ENKEPHALINS (Mu Receptors), which activate the RAPHE NEURONS

STEP 3:
- Axons from the Raphe Neurons travel to the Spinal Cord and release SEROTONIN, which Activate INHIBITORY INTERNEURONS, causing them to release OPIATES

STEP 4:
- The Opiates released by the Interneuron (Yellow) activate MU RECEPTORS on the Presynaptic Terminal of the C Fiber

STEP 5:
- This produces PRE-SYNAPTIC Inhibition that reduces the release of Substance P from the NOCICEPTOR (Blue) and REDUCES PAIN TRANSMISSION

Question 15

Qualities of Pain from Different Locations

Case 1

Answer 15

Medical Student Seuss was taking his FOM Final when, while turning pages of the Exam, he suffered a Paper Cut. There was a SHAPR PAIN when he FIRST sustained the Injury, but with time it has “Settled” to a DULL, ACHY PAIN

• The skin is Innervated by BOTH A Delta and C Fibers, leading to Fast, Sharp Pain at the time of Injury. However, the C Fibers (Group IV Fibers) were also activated, leading to the sensation of a DULL, ACHY Pain

MUSCLE PAIN:

• Cause: Usually Injury or Ischemia during Contraction
• Both Group III and IV Fibers Present
• Get BOTH FAST and SLOW Pain associated with Muscle

Question 16

Qualities of Pain from Different Locations

Case 2

Answer 16

Dr. K is her last attempt at dancing, exhibited her usual grace and has fallen on the Dancing Floor. She feels immediate pain that is associated with Muscle Spasms in her Right foot and leg. Attempts to bear weight on the affected foot are not successful:

• Dr. K has broken the Fifth Metatarsal, triggering activation of the DEEP Receptors, leading to Muscle Spasm and a Dull Achy Pain

DEEP PAIN:

• Associated with Periosteum, Ligaments
• Usually Dull, Achy
• Few A Delta Fibers
• Many C Fibers
• Associated with MUSCLE SPASM

Question 17

Qualities of Pain from Different Locations

Case 3

Answer 17

Louise R, a 75 y/o woman, reports Intense, Sharp pain in her Calf when she walks for long Distances. There is no Swelling, Redness, or Bruising in the area, and she reports no recent history of Injury

• Louise is suffering from INTERMITTENT CLAUDICATION, in which BLOOD FLOW to the Muscles in her legs is IMPEDED during EXERCISE. This creates ISCHEMIA and Local ACIDOSIS, which will activate the PAIN FIBERS embedded in her Muscles

VISCERAL PAIN:

• Poorly Localized
• Few Receptors
• Stretch Receptors
• OFTEN REFERRED!!!!!

Question 18

Muscle Pain

Answer 18

MUSCLE PAIN:
- Cause: Usually Injury or Ischemia during Contraction

• Both Group III and IV Fibers Present
• Get BOTH FAST and SLOW Pain associated with Muscle!!!!!!

Question 19

Deep Pain

Answer 19

DEEP PAIN:
- Associated with Periosteum, Ligaments

• Usually DULL, ACHY
• Few A DELTA FIBERS
• Many C FIBERS
• Associated with MUSCLE SPASM

Question 20

Visceral Pain

Answer 20

VISCERAL PAIN:
- Poorly Localized

• Few Receptors
• STRETCH Receptors
• OFTEN REFERRED!!!!!

Question 21

Referred Pain CASE 1

Answer 21

Ryan, a 15 y/o Male, ahs coem to your office because of a Tw-Day History of Abdominal Pain and Fever

When you ask him to show you where ti hurts, he points to the Upper Left Quadrants of his Abdomen. He feels pain when you Press on that area, but his Spleen is NOT ENLARGED

His fever is 101.5

**It is discovered that RYAN is suffering from PNEUMONIA!!!!

Question 22

Qualities of Pain from different Locations, Visceral Pain

Answer 22

• Early in life, many of our Experiences enable us to “Refine” the map that is Genetically coded in the Cortex…

This includes anatomically eliminating Synapses as well as Strengthening others

*** But Visceral Inputs didn’t get “refined” this way

Question 23

Qualities of Pain from Different Locations: REFERRED PAIN

Answer 23

• Previos Experience has taught the Brain that the Shoulder is more likely to EXPERIENCE PAIN than the Heart
• Confound this with the fact that the Nociceptors may converge on the same Interneuron in the Spinal Cord
• And the Brain is left with its “BEST QUESS”
• Which may be different if it has learned that a likely source of Pain is, instead, the neck or Jaw

RESULT:

• Ryna’s Pneumonia is confined to the LOWER LOWER of his Left Lung, which sites directly on the Diaphragm
• The Irritation of the Diaphragm produced by the PNEUMONIA was “Processed” by his Brain as LEFT UPPER QUADRANT PAIN

Question 24

Summary: Referred Pain

Answer 24

1) Identifying the EXACT LOCATION of a Stimulus requires experience on the PART of the Brain
2) VISCERAL PAIN si something we don’t experience enough to Process PROPERLY
3) There is also CONVERGENCE of the Fibers in the Spinal Cord
4) The END RESULT: Visceral Pain can be referred to some surprising places. The Prototypical Example is HEART ATTACK pain can be referred to the LEFT ARM, LEFT SHOULDER, and the JAW!!!