Pain Management In Anesthesia w. Dr. Derek Owens, Mary Baldwin University

Join the Free CSPA Community!

Connect with a network of Aspiring CRNAs, Nurse Anesthesia Residents, practicing CRNAs and CRNA Program Faculty Mentors here: https://www.cspaedu.com/community

Expand your understanding of pain management and anesthesia with the esteemed Dr. Derek Owens, DrAP, CRNA and Director of Curriculum for the Mary Baldwin University Nurse Anesthesia Program.

Dr. Owens guides us through the nervous system, starting with peripheral receptors and moving into the brain, explaining the role of sensory receptors in converting mechanical stimuli into electrical signals. He discusses the intricate pathways of pain transmission, including the dorsal column and anterolateral systems, and how these pathways influence the perception of pain.

With over 80 billion neurons in the CNS, Dr. Owens highlights the importance of synaptic connections and neurotransmitters in modulating pain signals. This episode is a must-listen for anyone in the Nurse Anesthesia field as Dr. Owens also touches on the role of local anesthetics and their impact on nerve fibers, providing insights into the latest advancements in anesthesia practice.

Also an Assistant Professor at the Mary Baldwin University Nurse Anesthesia Program, Dr. Owens brings a wealth of knowledge and experience to the table. With a career spanning diverse settings—from medical missions in the Philippines and Mexico to military surgical systems—Dr. Owens has positioned himself as an expert in acute surgical pain management.

Tune in now to unravel the complexities of the neurophysiology of pain, and gain a comprehensive understanding of how pain is perceived and managed in clinical settings. Also, be sure to check out the accompanying PowerPoint presentation on YouTube for a visual understanding of the concepts discussed.

Need Interview Prep Help In A Hurry? Fast-Track Your CRNA School Interview Prep with our CRNA Interview Crash Course! https://www.cspaedu.com/4wotmlds

Get access to application & interview preparation resources plus ICU Educational Workshops that have helped thousands of nurses accelerate their CRNA success. Become a member of CRNA School Prep Academy: https://cspaedu.com/join

Get CRNA School insights sent straight to your inbox! Sign up for the CSPA email newsletter: https://www.cspaedu.com/podcast-email

Book a mock interview, resume or personal statement critique, transcript review and more: www.teachrn.com

—

Watch the episode here

Listen to the podcast here

Neurophysiology of Pain & Pain Management in Anesthesia

Sensory Receptors & Neurons in the Central Nervous System

Hey everyone. My name is Derek Owens. I am faculty at the Nurse Anesthesiology Program at Mary Baldwin University in Staunton, Virginia. Today we’re going to talk about the neurophysiology of pain, at least getting started with that. I like to talk about things in some type of order, so we’ll talk about the nervous system starting from the peripheral receptors and back into the brain.

There are five basic types of sensory receptors. The goal of these receptors is to convert a mechanical stimuli into an electrical signal. This signal is then transmitted by nerve axons to different points in the central nervous system. The sensation that is felt when these nerve fibers stimulated is determined by where that axon terminates.

There are 80 to 100 billion neurons in the CNS. The incoming signal starts at the receptor and then enter the neurons through these synapses that are located mostly on neuronal dendrites and also on the cell body. There may be as many as 200,000 of these synaptic connections or maybe only a few hundred.

The output signal then travels via a single axon leaving the neuron to different places. This electrical energy is transmitted in the form of nerve action potentials. The transmission of these impulses can be blocked, changed, or integrated with impulses from other neurons. This typically occurs at nerve synapses.

So an action potential from the first neuron causes an opening of the voltage gated calcium channel that allows a large number of calcium ions to flow into the neuron. These calcium ions then bind to synaptic vesicles causing them to be released into the synaptic cleft. These released neurotransmitters act on receptor proteins on the next neuron to excite, inhibit, or modify its sensitivity in some way.

The Role of Neurotransmitters

There are more than 50 neurotransmitters, the most common of which are listed here (PowerPoint Presentation time stamp 4:21). Each neurotransmitter vesicle contains between 2,000 and 10,000 neurotransmitter molecules, and there are enough vesicles to transmit up to 10,000 action potentials.

The postsynaptic terminal has neurotransmitter receptors that either open an ion channel directly or activate a second messenger system. The specific ion channel that is open determines whether the neurotransmitter is excitatory or inhibitory based on whether it makes the ion more negative or it depolarizes. The ability to either excite or inhibit allows for either continued excitation or restriction, depending on the neurotransmitter that is released.

A little deeper dive into that: The normal resting neuronal membrane typically has a charge of negative 65 millivolts. By stimulating either sodium influx or potassium eflux, a neurotransmitter can stimulate hyperpolarization and diminished responsiveness or hypopolarization and continuation of the action potential.

A single presynaptic terminal on the surface of a neuron almost never excites the neuron. Many presynaptic terminals are required to be stimulated at the same time for these effects to be summated. This is called spatial summation, and you can see the negative 60 millivolts, which is around the resting membrane potential. Depending on whether you have sodium influx, it would make this number closer to zero and cause the potential to continue down the neuron. Or, potassium eflux would make this number more negative and decrease the impulse from continuing.

Understanding the Dorsal Column and Anterolateral Systems

Each of these neurons then synapses with other neurons to cause divergence or convergence of the signal. This can cause amplification with divergence or with multiple signals, can be combined into one to cause convergence. These signals then travel on either the dorsal column pathway or the anterior lateral pathway.

The dorsal column, medial lemniscal system, carries fine touch, vibration and pressure. There are three neurons. The first order ascends into the medulla. The second order crosses and continues to the thalamus and the third order projects from the thalamus to the cortex.

Pain Management in Anesthesia: There are at least three separate pathways for visceral pain; the visceral, parietal and vagus pathway.

Now the anterolateral system, it consists of the anterolateral tract, the spinalthalamic tract, the spinalreticular tract, and the spinalmesocephalic tract.

The anterolateral system is mainly for crude touch. The first order synapsis in the dorsal horn of the spinal cord at the level of the axon. The second order ascends to the thalamus or the periaqueductal gray depending on the tract. And the third order ascends to the somatosensory cortex.

The anterolateral system is comprised of smaller myelinated fiber that transmits signals at velocities from a few meters a second up to 40 meters a second. There’s less spatial orientation of the nerve fibers with respect to their origin and less spatial orientation of the signaling. That which does not need to be transmitted rapidly or with great spatial fidelity is transmitted through the anterolateral system.

Visceral Pain Pathways

Visceral pain is transmitted differently, though. There are at least three separate pathways for visceral pain; the visceral, parietal and vagus pathway. The visceral pain pathway follows the autonomic distribution. The parietal pain pathway stimulation is caused by skin over the organ. And lastly, the vagal nerve pathway is stimulated typically by hollow organs and causes nausea.

Pain receptors in the viscera are mostly chemo receptors that react to chemicals of inflammation as well as stretching. Visceral pain is transmitted via sensory fibers in the autonomic nerve bundles and the sensations are referred to the surface area of the body. They can sometimes be distant from the painful organ.

Parietal pain originates from the parietal peritoneal and the abdominal wall, and the pain is transmitted directly to the spinal nerves as sharp pain directly overlying the inflamed organ. Supraspinal sites for the termination of pain, neurons include the brainstem, the thalamus, the amygdala, and the cortex. There it’s processed, integrated, and modulated.

A large number of brain regions activated by noxious stimuli are referred to as the pain matrix. This accounts for the sensory, emotional and motivational aspects of pain.

The Complexity of Pain Perception

Pain is very complex. The thalamus is considered the relay station of the brain. It processes all sensory information except olfactory and modulates that sensory information to the cerebral cortex. It influences movement, motivating behaviors and alters levels of consciousness.

The ventral parts of the thalamus process information with high accuracy and then send it to the primary sensory cortices. The thalamus interacts with the periaqueductal gray and the periventricular areas to transmit signals down to the dorsal lateral columns where inhibitory inner neurons can block pain before it is relayed to the brain, and it is very important in pain suppression.

As we all know, pain varies tremendously with people, and this could partly be the result of the thalamus suppression or the thalamus lack of suppression.

So this descending pathway projects from the cortical regions of the brainstem, specifically through the periaqueductal gray and interactions with the thalamus, along with the rostral ventromedial medulla, which then project to the spinal cord to modulate afferent pain.

Descending Pain Modulation 

Descending pain modulation is the underlying mechanism for many interventions that we use, including surgical, psychological, and pharmacological interventions. Some of these descending loops, descending pain pathways can form loops where information can circulate in three to four separate descending systems.

Also, the vagal nerve plays a central role in pain modulation. The balance between inhibiting and facilitating signals from the brainstem plays a role in setting the gain of the pain signal processing in the spinal cord. The balance is controlled by different regions of the brain that are strongly affected by neuroplasticity.

Nerve Fiber Characteristics and Pain Transmission

Primary targeted, the descending pathways are cells and the dorsal horn of the spinal cord. All of this transmission occurs via nerve fibers that also have different transmission rates. This includes the fast, sharp pain signals, mechanical or thermal pain.

This fast signal serves to make a person react immediately while slow pain tends to become greater over time and makes the person continue to attempt to relieve the pain. So you can see the different speeds of these nerve fibers are listed here. (PowerPoint Presentation time stamp 10:50).

A little deeper dive into these nerve fibers: So some of these nerve fibers are myelinated while others do not have myelin. Myelin’s molecular structure is a lipid bilayer with a high ratio of lipids and includes integral and peripheral membrane proteins.

Interruptions in this myelin are called nodes of ranvier. A high density of voltage gated sodium channels are in this area, this interrupted area of nodes of ranvier. This means that these action potentials down the nerve axon continue via saltatory conduction.

Pain Management in Anesthesia: All of this transmission occurs via nerve fibers that also have different transmission rates. This includes the fast, sharp pain signals, mechanical or thermal pain.

They flow around these nodes of ranvier. Little energy is required to do this and it is rapid movement of action. Unmyelinated axons also have schwann cells as well, although the schwann cell doesn’t entirely envelop the nerve. The schwann cell can also contain multiple unmyelinated axons in a single schwann cell.

The Epineurium, Perineurium and the Endoneurium

A little deeper dive into that nerve tissue in these peripheral nerve fibers: These nerve fibers are held together by connective tissue that are organized into three distinct components. The epineurium is the outermost connective tissue.

The perineurium surrounds each nerve fascicle separately and individually, and then the individual nerve fibers are surrounded by the endoneurium. A dense layer of connective tissue is called the perineurium, which surrounds each fascicle and the epineurium encases the group. These nerve fibers are then surrounded by the schwann cells in either a myelinated pattern, or an unmyelinated pattern.

When local anesthetics are injected outside the epineurium, it must traverse both the epineurium and the perineurium to reach the axons and subsequently, only a small portion of the injected anesthetic comes in direct contact with the axon. This could lead to a delayed onset of the block, an incomplete block or no block.

At the same time, if you inject inside the endoneurium, you can cause decreased blood supply to the nerve and of course, pathology. This means of course, the Goldilocks location for the injection of local anesthetic is probably below the epineurium but above the endoneurium.

So an overview so far of what we’ve covered is the perception of pain involves the stimulation of neurons as well as nociceptors. The nociceptor is a primary afferent neuron that innervates the sites of stimulation. It’s attached to an axon that has a cell body in a spinal or dorsal root ganglia that terminates in the dorsal horn.

The second neuron projects from the dorsal horn to the thalamus and the third neuron projects from the thalamus to the sensory cortex. Supraspinal integration leads to complex sensory, emotional and motivational components that make up the perception of pain.

This includes the brainstem and modulation of the ascending nociceptive signal. There are projections from the brainstem to the spinal cord. They’re referred to as descending modulations and can be affected by therapeutic interventions.

So as we discussed before, nerve fibers are commonly classified according to their size, conduction velocity and function. A little bit more about the electrophysiology, and then we’ll dive into the local anesthetics.

Electrophysiology and the Central Nervous System

So the resting membrane potential in neurons is approximately negative 60 to negative 70 millivolts derived predominantly from a difference in the intracellular and extracellular concentrations of potassium and sodium ions. This gradient is maintained by protein pumps, cotransporters and channels via an ATP dependent process.

Action potentials are briefly localized spikes of a positive charge on the cell membrane caused by a rapid influx of sodium ions down the electrochemical gradient. When a certain threshold is reached, an action potential is triggered and further depolarization occurs in an all or none fashion.

An influx of potassium replaces the influx of sodium causing repolarization. A short refractory period after each action potential prevents the retrograde spread on previously activated membranes.

The most important channel or pump regulating this action potential is the voltage gated sodium channels, which are essential for the influx of sodium ions during the rapid depolarization phase. Local anesthetics block this sodium voltage-gated channel and the transmission of nerve impulses.

Local Anesthetics and Their Mechanism of Action

Local anesthetics reversibly bind to the intracellular portion of the voltage-gated sodium channels. To get to the site of action, these local anesthetics have to reach the target nerve membrane, meaning they have to diffuse through the lipid bilayer and then generate a concentration gradient on the inside of the tissues. 

Even with very close proximity, only one to 2% of the injected local anesthetic ultimately penetrates the nerve. The charge form of these local anesthetics then deactivatess, binds to the voltage-gated sodium channel.

So in summary, local anesthetics are injected close to a nerve. Only the unprotonated form can diffuse through the lipid bilayer once it gets inside the nerve. Once that unprotonated form diffuse inside the nerve, it then splits back into either the protonated or unprotonated form based on their chemical properties. And then the protonated form then binds to the voltage-gated sodium channel.

The most important chemical property of local anesthetics is the lipophilicity, the ability to diffuse through that lipid bilayer Share on X

Local anesthetics produce an order progression of sensory and motor deficits, usually starting with the disappearance of temperature sensation and ending with the disappearance of light touch. This is probably due to the expression of ion pores and channels on cellular membranes and different forms of sodium ion channels.

The most important chemical property of local anesthetics is the lipophilicity, the ability to diffuse through that lipid bilayer as we just discussed.

Systemic Absorption and Elimination of Local Anesthetics

Now we’re going to move on to systemic absorption. So systemic absorption of local anesthetic depends on the site of injection, the dose, the drugs that are used, the drug’s pharmacokinetic properties, and the utilization of a vasoactive agent.

Tissue vascularity has a very big influence on the rate of drug absorption, and you can see in this chart the different vascular sites absorb the local anesthetic at different rates. (PowerPoint Presentation time stamp 17:10).

Absorption leads to rapid redistribution throughout the body. A steady state drug concentration can be derived from the volume of distribution.

The pattern of distribution depends upon an organ’s perfusion, the partition coefficient between compartments and the plasma protein binding of the drug. Organs that are well perfused such as the heart and brain have higher drug concentrations.

Now for elimination, metabolic pathways for local anesthetics are determined by its chemical linkage. Esters are hydrolyzed by plasma cholinesterases and amides are transformed by hepatic carboxylaces and cytochrome P450.

Remember, hydrolysis is any chemical reaction that uses water to break one or more chemical bonds. That’s what happens to esters. Water causes breaking of the chemical bonds and it basically falls apart. And one way to remember, “amides have two eyes”, example, Lidocaine. Esters have one “i”.

Understanding Local Anesthetic Systemic Toxicity (LAST)

The accumulation of local anesthetics in the systemic circulation can cause local anesthetic systemic toxicity (LAST), which progresses through these symptoms: Analgesia to start, lightheadedness, tinnitus, numbness of tongue, seizures, then unconsciousness, eventually cardiovascular depression.

Cardiovascular toxicity is seen at high plasma concentrations and it can be potentially deadly. It correlates closely with potency and lipid solubility. All local anesthetics can cause hypotension, dysrhythmias, and myocardial depression. Although more potent agents such as bupivacaine, ropivacaine, and levobupivacaine are more likely to be associated with life-threatening outcomes such as cardiovascular collapse or a complete heart block.

How do you treat LAST, a systemic absorption? First is early recognition and rapid intervention. At the first sign of toxicity, stop administering the local anesthetic and get assistance. Seizures should be treated with benzos, hemodynamic management by ACLS protocols.

Cardiovascular collapse is dreaded. The one thing we’ve found to fix or to assist in repairing cardiovascular collapse is lipid resuscitation therapy. It used to be the only way that to repair this was cardiopulmonary bypass. Lipid agents or lipid resuscitation therapy has been found to save lives.

The clinical pharmacokinetics of local anesthetics are difficult to predict because both physical and psychological characteristics will affect the individual pharmacokinetics. There is some evidence for increased plasma levels in the very young and elderly that are caused by decreased clearance and increased absorption.

Summary of this is, and I can’t say this enough, is the correlation of systemic blood levels between the dose of local anesthetic and patient weight is often inconsistent and cannot not be used to predict toxicity. Although we use it regularly, we use weight-based dosing regularly, although it doesn’t correlate to cardiac toxicity.

So a very rapid journey today, we went through the anatomy of the nervous system, the neurobiology of nociceptive pain pathways. That included the thalamus descending control of pain. We then covered nerve histology, regional anesthesia, and local anesthesia.

We didn’t get to go over genotypes and phenotypes and how that affects pain. All of this information takes about a month to cover in anesthesia school, but luckily, you don’t have to listen to me that long, and so you just get the 20 minutes today.

A Brief History of Pain Theories

As one of my favorite podcasts says, we go back in time to understand how we got here. So what I want to leave you with, the last thing I want to say is, a brief summary of pain theories.

To start with, specificity theory is in 1662, Descartes described pain as a cord attached to a bell. By pulling on the end of the cord, the bell would ring. This is the classic drawing of a foot next to a fire.

A fundamental tenet of specificity theory is there is a dedicated fiber leading to a dedicated pain pathway connected to a sensory region in the brain. Different sensations stimulate different receptors, and each of these receptors causes a specific sensation in the brain.

This theory didn’t explain why sometimes pain persists after healing or why there were times when pain was sensed even though there was no injury. Plato defined pain as an emotion that occurs when the stimulus is intense and lasting.

In 1939, they proposed that a pain occurred in sensory systems when sufficient intensity was reached. So the intensity theory of pain. Experiments have summed this to be true, that repeated tactile stimulation below perception can actually produce pain.

Pain Management in Anesthesia: The sensation of pain is the result of the complex interaction of three components of the spinal cord.

These experiments led to what we know as temporal summation. We talked about that earlier, which is in medical physiology books today. This is the gain of pain circuits and pain systems.

The Gate Control Theory

The intensity theory said there’s no distinct pathway for low and high threshold stimuli. Rather, it was the number of impulses that differed between low and high threshold. In 1965, the gate control theory of pain revolutionized pain research by supporting both specificity and intensity theories.

It was proposed that there are nociceptors and touch fibers and these fibers synapse in two different regions of the dorsal horn of the spinal cord. The gate in the spinal cord is the substantia gelatinosa in the dorsal horn, which modulates the transmission.

When pain is sensed, it must travel to three locations in the spinal cord- cells in the substantia gelatinosa, cells in the dorsal horn, as well as fibers in the dorsal column. The substantia gelatinosa modulates the signals that get through. The sensation of pain is the result of the complex interaction of these three components of the spinal cord.

When the gate is closed, the brain does not receive the peripheral information and pain is not felt. This theory initiated the idea that pain was not solely the result of a physical injury, but rather a complex experience influenced by cognitive and emotional factors. This theory is still in use today.

The Biosocial Model (BPS) 

The biosocial model provides the most comprehensive explanation of pain. This theory hypothesizes that pain is a result of a complex interaction between biological, psychological, and sociological factors. The body cannot be divided into separate categories, and illness and disease are the result of complex interactions affecting an individual’s physical and mental wellbeing.

The thinking is that suffering is an individual’s emotional response to the nociceptive signals, and that pain behaviors are the actions that people carry out in response to this experience.

Pain has studied for centuries from Plato to current researchers. Each new theory has led us to a better explanation. Research will continue to move us forward as we utilize newer information to find the best treatments for our patients. Appropriately treating pain must be multi-dimensional and tailored to the individual experience. These are the references for this talk today; thank you for your time. (PowerPoint Presentation time stamp 24:03).

Mary Baldwin University Nurse Anesthesiology Program

I teach at the Mary Baldwin University Nurse Anesthesiology Program in Staunton, Virginia. We are 104 credit BSN to DNP 36 month full-time program of study. It’s a hybrid program, so there’s some online courses, in-person courses, and of course your clinical experience at the hospital in person. We have some regional clinical sites sprinkled throughout North Carolina, Virginia, and Maryland. Lots of simulation lab experiences, and you have an opportunity to participate in mission trips.

This is our program faculty (referencing PowerPoint Presentation time stamp 24:39): Dr. McPherson, the Program Director, Dr. Elmore is the Assistant Program Director. I am the Director of Curriculum. Dr. Wallace is the Director of Clinical Education. And Dr. Acord, the Director of Simulation. This is our program curriculum; Currently total 104 credits, 104 hours and total clinical hours of 2,400.

Year one is an online format, including synchronous and asynchronous courses. So we have scheduled times and we meet at certain times, but at least you could be in your own location. You don’t have to move the first year. Year two, we start in-person classes, so you have to move to Virginia or move closer. You of course, also start clinicals in year two. You start working on your DNP project and you’re doing simulations. Year three, full-time clinical training, preparing for your boards, your NCE exam, and you’re completing your DNP project.

So the overall program: year one is heavy didactic, including online synchronous asynchronous learning. Year two, you’re doing pretty heavy didactic and clinical training as well as simulations, and starting your DNP. Year three, you’re transitioning to full-time clinical training and completing your DNP. So that’s kind of the progression throughout the program.

Important dates for the program: The application cycle opens September 1st and closes December 15th. That’s through NursingCAS. In order to apply, of course you can see the application on NursingCAS, but you have to submit all your transcripts, your work history, a cv, a resume, personal statement, reference letters. We utilize the Casper situational judgment test, which is a computer-based test that you will take on specified dates.

As of the date of this recording, that only leaves a few left for this application cycle, so November 14th and December 5th. It’s important to get that scheduled so that you can apply. Otherwise, we welcome your applications. I look forward to reading all of your applications and reading about all the amazing things you’ve done, and will continue to do. Thank you.

—

Important Links

Join the Free CSPA Community! Connect with a network of Aspiring CRNAs, Nurse Anesthesia Residents, practicing CRNAs and CRNA Program Faculty Mentors here: https://www.cspaedu.com/community

Get access to application & interview preparation resources plus ICU Educational Workshops that have helped thousands of nurses accelerate their CRNA success. Become a member of CRNA School Prep Academy: https://cspaedu.com/join

Get CRNA School insights sent straight to your inbox! Sign up for the CSPA email newsletter: https://www.cspaedu.com/podcast-email

Book a mock interview, resume or personal statement critique, transcript review and more: www.teachrn.com

Learn More about the Mary Baldwin University Nurse Anesthesia Program: https://marybaldwin.edu/programs/nurse-anesthesiology-dnp/