BT_PM 1.5 Describe the injury response to acute pain

Townsville again

Another languishing LO. My feelings about this were “Ugh” and I wasn’t going to touch it either until I was looking through Acute Pain Management:Scientific Evidence, for another reason, and saw that there was a figure with that exact title – yippee!!

All statements relate to the figure (Fig 1.2 pg 26) and the surrounding text

Pain results in an decrease in activity of the parasympathetic nervous system T/F

Increased insulin sensitivity occurs in response to pain T/F

Cortisol levels are elevated by pain T/F

Activation of nociceptors results in changes in gene coding and protein synthesis T/F

In the post-operative setting it can be hard to separate the effects due to tissue damage from those caused by pain T/F

BT_PM 1.23 Describe the prostaglandin pathways and their physiological role in the production of pain

Townsville

There have been quite a few of posts on topics related to this one, but generally looking at how blockade of the PG pathway causes analgesia (ie. the effects of NSAIDs). I marked an SAQ on the effect of NSAIDs a couple of years ago. Candidates were much better at describing how these drugs produced their adverse effects rather than their beneficial ones.

So, how is it that prostaglandin production results in the experience of pain? Let’s investigate.

Although it is a pharmacology textbook, Katzung’s Basic and Clinical Pharmacology has an excellent chapter on prostaglandins (Ch 18). All of these statements are taken from that chapter. For those of you without access to the textbook, the beginning of this article has a good summary of how prostaglandins can produce pain.

BT_PM 1.23 Describe the prostaglandin pathways and their physiological role in the production of pain

COX 1 isoenzyme has a greater role to play in pain production compared with the COX isoenzyme T/F

Tissue damage releases cytokines which induce the COX-2 enzyme T/F

Arachidonic acid (the precursor of all prostaglandins) is induced by tissue damage T/F

PGE2 is involved in the sensitisation of peripheral nerve endings to painful stimuli, by reducing the threshold for neural transmission T/F

PGE2 has a role at the level of the dorsal horn to promote central sensitisation T/F

Hyperaemia in damaged tissues results from increased vascular permeability mediated by prostacyclin T/F

Hyperaemia enables increased delivery of inflammatory mediators to the area of tissue damage, resulting in further prostaglandin release T/F

BT_PM 1.12 Describe opioid receptors

I don’t have any nice new poppy photos, so we will go with a water lilly instead

I think this is another LO where you what you learn should be directed towards how it affects function rather than just memorising in detail the intricacies of the receptor itself.

The top 4 statements are core. The last one is the most interesting (I’ll try to find a good concise article on it for those who are interested and will update the post when I have). You will find the answers to the rest in, you guessed it, Hemmings and Egan 2e. There is also a nice summary article in BJA Education here.

BT_PM 1.12 Describe opioid receptors

Opioid receptors are G-protein coupled receptors  T/F

Opioid receptors are found only on post synaptic cell membranes T/F

Activation of opioid receptors increases potassium conductance and  causing membrane hyperpolarisaton T/F

All opioid receptor subgroups have their own endogenous ligand, with B endorphin the ligand for the mu opioid receptor T/F

Opioid receptors are subject to significant genetic polymorphism which effects nociception and analgesia T/F

BT_RA 1.7 Describe the pain and sensory pathways

T/F  the sensory pathway (including pain) consists of three separate neurons: 1. periphery to spinal cord, 2. spinal cord to thalamus, 3. thalamus to cortex (see also Discussion Point 1)

T/F  sharp, well localised pain is transmitted via A-delta nerve fibres

T/F  C fibres are polymodal, and respond to thermal, chemical and mechanical stimuli

T/F  C fibres synapse in the dorsal horn at laminae I and II

T/F  all sensory information (including pain) is transmitted in the spinal cord via the spinothalamic tract

T/F  the primary sensory cortex (in the brain) lies anterior to the primary motor cortex

References:

  1. Kam & Power 3rd edition Chapter 13
  2. Ganong 24th Edition Chapter 8

Discussion Point 

  • does this basic scheme still apply for sensation/pain transmitted via cranial nerves?

IT_PM 1.3 Outline the basic concepts of multimodal analgesia and pre-emptive analgesia

T/F  multimodal analgesia involves the use of a combination of analgesic drugs which each have a different mode or site of action

T/F  multimodal analgesia can: (i) improve the quality of analgesia, and (ii) reduce opioid use, thereby limiting opioid induced side effects

T/F  an opioid is always needed for multimodal analgesia to be effective

T/F  The concept of pre-emptive analgesia involves giving analgesic drugs prior to skin incision. This emerged from animal studies which showed that this technique minimised dorsal horn changes associated with central sensitisation. However, in clinical studies, there are conflicting outcomes when comparing “pre-incisional” and “post-incisional” interventions.

T/F  epidural analgesia is one intervention which has a clear pre-emptive analgeic effect

T/F  The concept of pre-emptive analgesia has largely been replaced by the concept of preventive analgesia. This refers to interventions which can reduce peripheral and central sensitisation, and thereby reduce the intensity and duration of post-operative pain (compared with other interventions, or no intervention). Preventive analgesia is not defined by the timing of the intervention.

T/F  preventive analgesic effects can be produced by – local anaesthetics (regional and neuraxial), ketamine, and gabapentin

Reference
APM-SE (2015), Chapter 1, Chapter 8

BT_PM 1.3 Pre-emptive and preventive analgesia

poppies

Glass poppies Andy Paiko

 

A few weeks ago I ran a series of posts on this LO.

I ran out of steam before reaching the last of the bullet points. This was partly because the area has held so much hope from a theoretical mechanistic viewpoint but there is little strong scientific evidence to support benefit from particular clinical practice – how disappointing….

I thought it might be timely to revisit now, just before the written exam. I wish there were a rapidly acting pre-emptive analgesic, I could prescribe, to make tomorrow less painful for those of you about to sit. However, the best prescription, to make the day easier, is to have studied well and practised lots – which I am sure all of you who read this blog will have done. BEST WISHES!!

The latest edition of Acute Pain Management: Scientific Evidence has a section on this topic (I hope that link takes you there. If it doesn’t, the book is freely available here [see section 1.5]).

BT_PM 1.3  Describe the basic physiological mechanisms of pain including:

· Pre-emptive and preventive analgesia

Pre-emptive analgesia, by definition, must be given before a noxious stimulus occurs TRUE/FALSE

The aim of pre-emptive and preventive analgesia is to reduce sensitisation   TRUE/FALSE

The NMDA receptor plays an important role in central sensitisation  TRUE/FALSE

Peri-operative ketamine infusions may have a role in preventing the development of chronic post-surgical pain    TRUE/FALSE

Outcomes in this area have been muddied by fraudulent research   TRUE?FALSE

BT_PM 1.3 Describe the central processing of pain

In the protracted series on this LO, today we have made it to the brain. Again a complex area, but one where it is important to have some fundamentals sorted in your minds.

Version 2

I thought you might need something beautiful today as an antidote to all the pain… Here is the inverted dome ceiling of the Palau de la Musica in Barcelona. The whole building is amazing and the ceiling even more sublime in person

BT_PM 1.3  Describe the basic physiological mechanisms of pain including:

• Central processing of pain

 

Nuclei in the lateral thalamus mediate the processing of the sensory and discriminative aspects of pain   TRUE/FALSE

The amygdala is involved placing pain within an emotional context, which may enhance to inhibit the pain experienced     TRUE/FALSE

The primary somatosensory cortex is involved with both sensory and emotional processing of pain    TRUE/FALSE

Nuclei in the medial thalamus have projections to areas involved with the affective experience of pain      TRUE/FALSE

At the level of the brainstem, and through associated neural networks, there is modulation of the autonomic response to pain  TRUE/FALSE

BT_PM 1.3 Describe the physiology of signal conduction in relation to pain

I am going to interpret this as signal conduction from the periphery to the brain, in other words, conduction along the primary and secondary (or projection) afferents.

IMG_3603

This is definitely an area where you don’t want the wires getting crossed…… (photo Ho Chi Minh City)

BT_PM 1.3  Describe the basic physiological mechanisms of pain including:

· Conduction

 

Voltage gated sodium channels are important in normal and abnormal transmission of signals along the primary afferent neurone  TRUE/FALSE

Increased potassium conductance in the primary afferent neurone will tend to enhance signal transmission    TRUE/FALSE

Nociceptive-specific projection afferents predominate in Rexed lamina I and respond exclusively to noxious stimuli   TRUE/FALSE

Wide dynamic range neurones receive input from visceral and somatic sources TRUE/FALSE

Activation of NMDA receptors, on the post synaptic membrane, occurs readily at normal signal transmission strength TRUE/FALSE

BT_PM 1.3 Describe the physiology of spinal cord modulation of pain

Rather than asking what can happen to the pain signal at the spinal cord, perhaps we should ask what doesn’t happen!!

This is a complex area, but it is important to understand some basic principles…

OLYMPUS DIGITAL CAMERA

This pretty crumby photo of the maze at Schloss Schönbrunn reminded me of today’s topic…

BT_PM 1.3 Describe the basic physiological mechanisms of pain including:

· Spinal cord modulation

 

In the dorsal horn, both inhibitory and excitatory interneurones may synapse with the primary afferent   TRUE/FALSE

GABA is an important neurotransmitter of inhibitory interneurones  TRUE/FALSE

Virtually all primary afferents exert their excitatory effects on postsynaptic structures by the release of glutamate TRUE/FALSE

Opioid receptors are found pre- and post-synaptically on neurones in the dorsal horn TRUE/FALSE

Descending inhibitory pathways exert their influence at the dorsal horn   TRUE/FALSE

 

There are some more relevant statements at this post  from early 2017

Over at aGasgal, I have put up a couple of  my favourite simple diagrams related to pain pathways.

 

BT_PM 1.3 Physiology of peripheral nociception

Happy new year to everyone. I hope that the first days of 2018 have treated you kindly.

There are quite a few LOs on the neurobiology of pain, but not many posts here on the topic (I’m not surprised….)

OLYMPUS DIGITAL CAMERA

Above is a poppy ( complete with bumble bee) taken at Port Arthur, where I suspect a lot of pain was both felt and inflicted….

I have taken today’s statements from Hemmings and Egan’s book which has quite a good chapter on nociceptive physiology.

BT_PM 1.3   Describe the basic physiological mechanisms of pain including:

· Peripheral nociception

 

Activation of peripheral opioid receptors reduces the likelihood an nociceptive signal being transmitted       TRUE/FALSE

Nocioceptors have both afferent and efferent functions TRUE/FALSE

Endogenous ligands of nociceptors include bradykinin and 5-HT    TRUE/FALSE

Primary hyperalgesia can occur when peripheral nociceptors are sensitised TRUE/FALSE

Each nociceptor responds to a single ligand/stimulus    TRUE/FALSE