Tuesday, March 25, 2008

Pre-emptive Analgescis--what is he talking about now?

Z Health R Phase Certification in MN this weekend!
Just a heads up for anyone that is one the fence, that the R Phase Cert is here this weekend! There is currently an awesome group of people signed up and it will be a blast! I will be there all day Sat and Sun and I am sure I will learn new stuff again even though this will be my third time through the first 3 days. Basics are best!

The Pain Train Continues
If you missed the last post on pain, see the one before this and check it out. Below is another guest post from Nicole Nelson in relation to pain. Ok, so I am biased since she is my sister, but the information is great and there is a bit about how it relates to Z Health and movement towards the end also. She is currently at the U of MN working on her advanced degree to be a c
ertified registered nurse anesthetists (CRNA)--those people that put you as close to death as possible during a procedure and make sure you come back too!

Pre-Emptive Analgescis

by Nicole Nelson, RN

Chronic pain affects millions of people in the world today. As an anesthesia provider it is crucial to know how to adequately treat pain in a multi dimensional approach. One way anesthesia providers may decrease post operative pain is by giving pre-emptive analgesics. Decreasing pain at the spinal level is a good approach to both acute and chronic pain. Research of the pain pathways is complex and new thinking has shown that it is a multi sensory system according to the neuromatrix of pain (Mosely, G. 2003).

Pain can be difficult to define since everyone perceives and experiences pain differently. According to the definition by Morgan, Mikhail and Murray, pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage (Morgan, Mikhail, & Murray 2006). Pain is categorized as either acute or chronic. Post operative pain is considered acute pain and is usually due to nociceptive stimulus. Chronic pain on the other hand is when acute pain fails to be resolved from either abnormal healing or inadequate treatment. Chronic pain may be nociceptive, neuropathic or mixed (Morgan, Mikhail and Murray 2006). A recent article by Weiss, Vanderlin and Hietpas states that chronic pain is the nation's leading cause in adult disability (Weiss, M., Vanderlin, D., Hietpas, J. 2007).

Physiologic pain pathways can be very complex and only a brief overview will be provided here. When a pain receptor is stimulated it travels to the CNS by two neurons known as either A-delta or C nerve fibers. The A-delta fibers are large in diameter, fast conducting myelinated fibers which transmit "first" pain experienced as sharp, prickling and injurious ( Kelly, D., Ahmad, M., Brull, S. 2001). The C fibers are small in diameter, slower conducting unmyelinated fibers that are responsible for "second" pain experienced as dull, aching and visceral type ( Kelly, D., Ahmad, M., Brull, S. 2001). The sensory neurons then travel to the spinal cord and synapse with second order neurons located in the dorsal horn. The second order neurons then travel either up the spinothalamic tract or ipsilateral spinal pathway to the thalamus. Once the impulse arrives in the thalamus it is sent to other CNS centers such as the somatosensory cortex. These higher centers are responsible for the perception of pain and the emotional components that accompany it (Kelly, D., Ahmad, M., Brull, S. 2001). In the sensory pathway there are four distinct steps in the transmission of painful stimulus known as: transduction, transmission, modulation and perception. It important to understand each area since each step is a potential target for analgesic therapy. Transduction is a process where nociceptors respond selectively to noxious stimuli and convert chemical, mechanical or thermal energy at the site of the stimulus into neural impulses (Kelly, D., Ahmad, M., Brull, S. 2001). The intensity of the impulse arriving in the dorsal horn depends on how much excitatory or inhibitory transmitter is released. Transmission occurs once the signal has arrived in the dorsal horn and where it synapses depends if the signal is coming from an A-delta or C nerve fiber. The A-delta neurons synapse in laminae I, II and V, and the C fibers in laminae I and II (Widmaier, E., Raff, H., Strang, K. 2006). Neurotransmitters are released and can cause changes in the excitability of the cell. In addition to causing increased excitability to the cells, repeated noxious stimulation of the dorsal horn may result in an increase in the number of neurons in laminae I and II whose nuclei express C-fos protein, a protein thought to be involved in the memory of pain ( Kelly, D., Ahmad, M., Brull, S. 2001). This is one area in which preemptive analgesic such as morphine could decrease the number of cells expressing C fos protein. The next step in the sensory pathway is known as perception. This step involves the impulse leaving the dorsal horn and traveling up to the thalamus then on to the somatosensory cortex. Analgesic therapy has traditionally targeted the pain perception component of the analgesic pathway (Kelly, D., Ahmad, M., Brull, S. 2001). By understanding each concept in the pain pathway it allows providers to use several different analgesic agents which each act on a specific area in the pain pathway.

As stated earlier, treatment of either acute or chronic pain involves a multi-dimensional approach. Preemptive analgesic may be one way to treat acute pain before it can trigger long-term neuronal changes leading to chronic pain. Some of the neuronal changes in chronic pain involve a term known as "wind up" that occurs when the initial pain stimulus goes on too long and the NMDA receptors become sensitized (Kelly, D., Ahmad, M., Brull, S., 2001). This then triggers a cascade of events that leads to CNS hypersensitization. This process can lead to a long line of complications from pain such as hyperalgesia, non-pain nerves begin to fire and carry pain messages, the threshold of opiod receptors is increased, sensitivity to catecholamines is lowered and the pain fields spread to adjacent neurons in the spinal cord (Copstead, L,. Banasik, J. 2005). The long line of complications and neural changes that occur from chronic pain only reinforces why acute pain should be treated aggressively. As researchers develop a better understanding of acute pain mechanisms it has been shown in clinical trials that preemptive analgesic could benefit the patient with decreased postoperative pain, decreased hospital stays and improved overall satisfaction of care (Turan, A.,White, P., Karamanlioglu, B., Pamukcu, Z. 2007). Preemptive analgesia is defined as analgesia given before the initiation of nociceptive stimulus (Pyati & Gan, 2007). There still remains a lot of controversy over preemptive analgesia. A recent review of literature by Pyati and Gan in 2007 demonstrated that around 40% of studies showed a beneficial effect (reduction in pain and analgesic consumption) of pre-incision analgesia as opposed to analgesic administration after surgical incision ( Pyati & Gan, 2007). There are many factors that play a role in preemptive analgesia such as which drug is given, dosage and duration of medication and the exact time that the medication was given preoperatively. Gabapentin is just one of many medications a provider could give as a preemptive analgesic. Gabapentin has primarily been given as an anticonvulsant but it is also used extensively in the treatment of neuropathic pain. It works primarily on voltage dependent calcium channels, resulting in postsynaptic inhibition of calcium influx and which will reduce presynaptic excitatory neurotransmitter release (Pyati & Gan, 2007). Research has now shown gabapentin is helpful in reducing the central neuronal sensitization that occurs in postoperative pain (Turan, A., White, P., Karamanlioglu, B., Pamukcu, Z. 2007). In one particular study by Pyati and Gan in 2007 demonstrated a reduction in morphine consumption post operatively by 32% when 3 grams gabapentin was administered before and during the first 24 hours after abdominal hysterectomy (Pyati & Gan, 2007). In another study with inflammatory pain, gabapentin was shown to reduce hyperalgesia and inhibit C-fiber response to noxious stimuli by modulating both central and peripheral nociceptive response (Turan, A., White, P., Karamanlioglu, B., Pamukcu, Z. 2007). Lastly in a study by Turan, White, Karamanlioglu and Pamukcu in 2007 it showed the effects of tourniquet pain from a total knee surgery. Gabapentin decreased postoperative pain as much as 50% in the controlled group (Turan, A., White, P., Karamanlioglu, B., Pamukcu, Z. 2007).

Preemptive analgesic is the first step in controlling acute post surgical pain and including ideas evolved from the pain neuromatrix may be an insight into controlling chronic pain. The pain neuromatrix was developed over a decade ago by Melzack and Wall (Moseley, 2003). Melzack and Wall developed the ideas in the pain neuromatrix on the bases that pain is produced by the brain when it receives neuronal signals that danger to body tissues exists and that there needs to be an action (Mosely, 2003). There are four basic concepts within the neuromatrix. The first concept is that pain is produced by the brain (Mosely, 2003). The second concept is that pain is produced when the brain perceives that danger to body tissues exists and action is required (Mosely, 2003). Third concept consists that pain is part of the survival system, any threat, can be interpreted as pain (Mosely, 2003). The last concept is that pain is individual (Mosely, 2003). In traditional ideas of pain it is perceive that pain is caused by a physical injury. The main difference between traditional ideas and the neuromatrix is that pain can be caused by a physical injury but pain can also be stimulated within the body by either a noxious or non-noxious threat. Acute pain is generally well understood but chronic pain syndromes, which are often characterized by severe pain associated with little or no discernible injury or pathology, remain a mystery (Melzack 2003). Melzack states, "chronic pain is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology. A great study by Onodera, Shirai, Miyamoto and Genbun in 2003 looked at the density and distribution of neural endings in rabbit lumbar facet joints after anterior spinal fusion and to evaluate the effects of intervertebral immobilization. The author states, "These results suggest that immobilization of the intervertebral segment causes a reduction in the number of mechanoreceptors in the facet joint capsules because of the reduction in mechanical stimulation. Moreover, in the upper adjacent facet joint there may be neural sprouting caused by nociceptive stimulation" (Onodera, Shirai, Miyamoto and Genbun 2003). One simple way to apply this idea is to think about when you accidentally burn your finger on a hot stove. According to the ideas in the neuromatrix the actual pain is considered an action signal so you pull your hand away to decrease the threat, then you might franticly wave your hand around to decrease the pain by increasing mechanoreceptor stimulation. Another example is to apply other systems such as the Z Health Performance System to the neuromatrix. Z Health uses joint mobility exercises to increase mechanoreceptor stimulation and therefore potentially reduce chronic or acute pain.

The ideas involving pain physiology are very complex. Preemptive analgesic may be just one way of many to help prevent acute postoperative pain. Using a multi sensory system such as the neuromatrix of pain could be another way to treat chronic pain and trigger new non-painful neural pathways. Including all the concepts in pain physiology and add the ideas of the neuromatrix may lead to a new way of thinking on how to treat acute and chronic pain in the near future.


Copstead, L., Banasik, J. (2005). Pathophysiology 3rd edition. St. Louis: Elsevier Saunders

Kelly, D., Ahmad, M., Brull, S. (2001). Preemptive analgesia I: physiological pathways and pharmacological modalities. Regional Anesthesia and Pain, 48(10), 1000-1010.

Melzack, R. Pain and the neuromatrix in the brain. Department of Psychology, McGrill University, Montreal, Canada. rmelzack@ego.psych.mcgill.ca

Morgan, E., Mikhail, M., Murray, M. (2006). Clinical Anesthesiology. New York: Lange Medical Books/McGraw hill.

Moseley, G. (2003). A pain neuromatrix approach to patients with chronic pain. Manual Therapy

Onodera, T., Shirai, Y., Miyamoto, M., Genbun, Y. (2003). Effects of anterior lumbar spinal fusion on the distribution of nerve endings and mechanoreceptors in the rabbit facet joint. Journal Orthopedic Science, 8(4), 567-576.

Pyati, S., Gan, T. (2007). Perioperative Pain Management. CNS Drugs, 21(3), 185-211.

Turan, A., White, P., Karamanlioglu, B., Pamukcu, Z. (2006). Premedication with Gabapentin: The Effect on Tourniquet Pain and Quality of Intravenous Regional Anesthesia. Brief Report-International Anesthesia Research Society, 104(1), 97-101.

Weiss, M., Vanderlin, D., Hietpas, J. (2007). Controlling Chronic Pain in the Workplace- Nerve Stimulation and Intrathecal Drug Delivery Systems. Continuing Education, 55(11), 463-467.

Widmaier, E., Raff, H., Strang, K. (2006). Vander's Human Physiology. New York: McGraw Hill.