B&b Week 6 Lecture 1

Front 1

What is Pain?

Back 1

multidimensional sensory experience that is intrinsically unpleasant and associated with hurting and soreness

Front 2

Define hyperalgesia

Back 2

An increased response to a normally painful stimuli.

Front 3

Define allodynia?

Back 3

A painful response to a normally benign stimulus.

Front 4

What is chronic(neuropathic ) pain?

Back 4

Pain that persists after the temporal course of natural healing due to central sensitization.

Front 5

2 challenges to pain management:

Back 5

1) Identify the mechanisms responsible for producing hypersensitivity to pain.
2)Find means of normalizing sensitivity or preventing hypersensitivity from becoming established

Front 6

2 mechanisms involved in hypersensitivity:

Back 6

1)Peripheral
2)Central

Front 7

Activated neutrolphils at a site of tissue injury contain activated COX-2 enzyme which is responsible for the production and secretion of what?

Back 7

Prostaglandin E2 which reduces the threshold of activation and increases the responsiveness of nociceptor terminals, by binding to the prostaglandin E receptor. (this is peripheral sensitization)

Front 8

What is the basic process of peripheral sensitization?

Back 8

Inflammatory chemicals/mediators cause changes in key nociceptive receptors and ion channels that determine neuron excitability

Front 9

What are two processes implicated in peripheral sensitivity?

Back 9

1)Post-translational
-typically phosphorylation of receptors/channels thus lowering threshold of opening or duration of opening; local effect
2)Altered gene expression
-signals cause transcription or translation to be altered

Front 10

What is the basic process of central sensitization?

Back 10

Increased excitability of CNS neurons, so that normal inputs produce abnormal responses.

Front 11

What 2 things occur after the acute phase of central sensitization?

Back 11

1)Increased phosphorylation of channels/receptors
2) Increased insertion of channels/receptors into the membrane

Front 12

During central sensitization what changes occur to the glutamate activated NMDA receptor?

Back 12

-phosphorylated: which helps it distribute from intracellular to the synaptic membrane and increases its responsiveness to glutamate

Front 13

What causes the NMDA receptor to be more responsive to glutamate?

Back 13

removal of voltage dependent Mg2+ ion block, so that channel stays open longer

Front 14

What is ketamine?

Back 14

NMDA receptor antagonist. So it decreases excitability of postsynaptic terminal. Used as a short acting anasthetic, but has many side effects centrally.

Front 15

What happens during the persistent phase of central sensitization?

Back 15

1) Gene regulation.
-Local:Increased transcription and translation of receptor genes
-Globally genes are upregulated for example by COX-2 expression in CNS neurons post injury which causes production of prostaglandin E2
2) Disinhibition
-reduced inhibitory transmitter, loss of inhibitory interneuron, altered descending modulation from brain

Front 16

What is the gate theory?

Back 16

The transmission of pain from the peripheral nerve through the spinal cord can be altered by: other afferent neurons or controls emanating from the brain.

Front 17

What does stimulation of the periaqueductal gray matter do to the sensation of pain?

Back 17

It can produce analgesia by causing stimulation of inhibitory neurons that suppress the transmission of pain in the laminae of the spinal cord.

Front 18

What is the theory behind using TENS for pain relief?

Back 18

Transcutanaeous electrical stimulation is thought to activate A-beta fibers which reduces the flow of pain info to brain

Front 19

What happens in the persistent phase of central sensitization during structural reorganization?

Back 19

C fibers atrophy, creating vacant synaptic sites in dorsal horn, interneurons also die. A-beta touch fibers inappropriately grow into these zones so that peripheral normal touch stimulates pain.