Pathophysiology of Pain:

Implications for Perioperative

Nursing
LES RODRIGUEZ, MSN, MPH, RN, ACNS-BC, APRN

ABSTRACT
The pathophysiology of pain is a complex process that varies according to duration (eg, acute, chronic)
or type (eg, nociceptive, neuropathic, psychogenic). Perioperative nurses should understand the
pathways that lead to pain to better assist in managing patients pain symptoms. Approaching pain
from a patient-centered stance includes acknowledging that pain is dened entirely by the subjective
experience of the patient, which may not be proportional with the level of tissue damage. This article
provides a brief description of the pathophysiology of pain and the components of nociceptive and
neuropathic pain pathways to aid the perioperative nurse in pain management. AORN J 101 (March
2015) 338-344. AORN, Inc, 2015. http://dx.doi.org/10.1016/j.aorn.2014.12.008
Key words: pain pathway, nociceptive pain, neuropathic pain, psychogenic pain, acute pain, chronic
pain.

http://dx.doi.org/10.1016/j.aorn.2014.12.008
AORN, Inc, 2015

338 j AORN Journal

www.aornjournal.org

March 2015, Volume 101, No. 3

ain is both a health care issue and a pervasive physical

disorder that has been poorly understood until
recently.1 Philosophical, political, and religious
implications of pain have paralleled the distress of human
beings for much of human history. During the 1600s,
French philosopher, writer, and mathematician Rene
Descartes
(1596e1650)
rst
described
detailed
somatosensory pathways, or a link between peripheral
sensation and the brain. He hypothesized that pain traveled
through only one pathway, believing this same pathway was
also used by other sensations. His published manuscript
Treatise of Man described pain perception existing in the
brain, where it creates differences between neural occurrences
of sensory transduction and the perceived understanding of
pain.2,3 Simply put, sensations stimulated in the body are
sent directly to the brain, where they are actually perceived.
Although appearing overly simplistic in its description,
Descartes was a visionary in his insightful realization that
sensory perception is a function of the brain. His view of
the pain processes set the foundation for a robust
understanding of the pain process that enables us today to
manage patients pain much more effectively.

DEFINITIONS OF PAIN
In pain literature, two denitions are considered to be highly
descriptive of the duality of pain. The rst broadly accepted
denition originates from the International Association for the
Study of Pain (IASP). The IASP denes pain as an unpleasant
sensory and emotional experience associated with actual or
potential tissue damage, or described in terms of such damage.4(p5) This denition refers to pain as a sensation with
numerous mechanisms that affect a persons psychosocial
and physical functioning. It acknowledges the complexity of
the pain experience and the awareness that pain is not
caused by tissue and organ damage alone. There is no
predictable relationship between identiable tissue injury and
the sensation of pain.5 At times, a patients description of
the level of pain may be inconsistent with the actual
evidence of tissue damage. This presentation is sometimes
seen in the trauma patient who may be severely injured but
remains awake, alert, and oriented and does not complain of
much pain. In some instances, pain may be caused by
abnormalities in the neural processing of stimuli; therefore, a
lack of tissue damage may not correlate with an absence
of pain.5
Pain clinician and expert Margo McCaffrey, MS, RN, FAAN,
developed a more clinically useful denition of pain, which
acknowledges that pain is an individual and subjective

www.aornjournal.org

Pathophysiology of Pain

experience. She describes pain as whatever the experiencing

person says it is, existing whenever he says it does.5(p5) This
denition places the patient at the center of the experience
and establishes the patients self-report as a reliable indicator
of the level of pain.

CATEGORIES OF PAIN
Pain may be categorized by duration (eg, acute, chronic), type
(eg, nociceptive [awareness], neuropathic, psychogenic), site
(ie, muscle, joint, visceral), or etiology (eg, trauma, disease).
Patients may experience more than one type of pain simultaneously. For the purposes of this article, duration and type of
pain are discussed.

Duration of Pain
Acute pain is a time-limited unpleasant experience with
emotional, cognitive, and sensory features, resulting from tissue trauma or damage. This type of pain is usually associated
with signicant observable tissue pathology and routinely resolves with healing. However, acute pain that is inadequately
treated can lead to long-term changes in the nervous system,
chronic pain, and psychological distress.6,7 Acute pain also
involves biological functions that protect against further injury.
For example, pain produces protective reexes, including an
unconscious withdrawal from the noxious stimulus, muscle
spasms, and other autonomic reactions such as ight. Acute
pain is usually categorized as pain lasting up to six
months duration.8
Chronic pain persists beyond the expected recovery period
after the trauma or injury (eg, surgery for diseased tissue),
usually lasting more than six months.8 Often, the identiable
pathology creating this type of pain is insufcient to explain
the persistent pain. Chronic pain is disruptive to sleep
patterns and activities of daily living and as a pain syndrome,
it serves no protective or adaptive function.

Type of Pain
The process of pain awareness is nociception. Nociceptive pain
results from tissue destruction (ie, direct invasion), inammation, or injury. Nociceptive pain occurs when noxious
stimuli activate the afferent neurons (ie, nerves that transmit
impulses by receptors to the central nervous system). Nociceptors are highly specialized sensory neurons that detect
injury and tissue damage. Some examples of nociceptive pain
include a paper cut on the skin, a femoral fracture, discomfort
in the course of a cancerous tumor, or chest pain during a
myocardial infarction. The process of nociception occurs
AORN Journal j 339

Rodriguez

March 2015, Volume 101, No. 3

through four phases: transduction, transmission, perception,

and modulation:

Phase 1: Transduction. Transduction begins in nociceptors that
are located in the skin, joints, and walls of organs. Categories of
nociceptors fall into four groups, which include thermal, mechanical, polymodal, and silent. Silent nociceptors are free nerve
endings that react poorly to all stimuli. These receptors convert
noxious stimuli (eg, incising the skin with a scalpel) into an
electrical current by transduction, which begins when damaged
cells release nociceptor-sensitizing substances such as bradykinins, histamines, prostaglandins, serotonins, and substance
P.5,9,10 Substance P (eg, tachykinin or transmitting neuropeptide)
is discharged from terminals of specic sensory nerves found in
the brain and spinal cord. Substance P is also associated with
inammatory processes. The nociceptor-sensitizing substances
generate a current, known as an action potential (ie, a
momentary change in electrical membrane potential on the
surface of a cell rapidly increases to a 40 mV and just as rapidly
decreases to a 90 mV, resulting in an nerve impulse).

Phase 3: Perception. When pain is perceived, electrical impulses cause neurotransmitters to release from nociceptor
endings in the brain, triggering relay signals across the synapses to dorsal horn neurons. Neurotransmitters are chemicals that communicate signals across a synapse from one
neuron or brain cell to another target neuron. The transmitted signal from the dorsal horn neurons is then sent using
ascending nociceptive pathways to higher axes in the brain,
where it is perceived as pain (ie, the conscious awareness of
discomfort). The perception process further interprets the
signal into specic sensations (eg, sharp, burning,
pressure).3,5,9,10

Phase 4: Modulation. Governing structures located in the
dorsal horn area of the spinal cord modulate ascending
nociceptive transmissions. Neurons located in the lower brain
stem regulate this modulation. During the modulation process, nociceptive impulses transmit through dorsal horn projections in the spinal cord. The spinal cord then releases
substances such as serotonin (5HT), endogenous opioids (eg,
enkephalins, endorphins), and norepinephrine. This process

Only microseconds are required for the signal

to be conducted from the site of injury to the
brain, where pain is perceived.

Phase 2: Transmission. The action potential continues from

where it generates and transmits along nociceptive axons (ie,
nerve bers) to cell bodies in the dorsal root ganglion found
in the spinal cord and then to the central terminals located in
the dorsal horn at the base of the brain. An action potential
creates a depolarization event. Depolarization follows a
consistent path, during which potassium exits the cell and
sodium enters it, changing the cells electrical polarity and
resulting in the conduction of the signal. One of the easiest
representations of this is a subway car. Each car represents a
cell along a rail track (ie, myelin sheath). Each time the doors
of the car open, potassium exits the car onto the platform
and sodium enters from the platform into the car. When
pain occurs, the nerve communicates the impulse along
neurological pathways (eg, similar to the connection between
the cars on the subway train), and the process of nerve
communication is repeated until the impulse or message
reaches the end of the line (ie, the brain). Only microseconds
are required for the signal to be conducted from the site of
injury to the brain, where pain is perceived.
340 j AORN Journal

of modulation, ending in the release of these substances, serves

to decrease or downregulate the pain response.11,12 For
example, when an individual rst experiences a minor injury
(eg, a cut or burn), there is the immediate sensation of intense
pain that quickly modulates to a much more manageable
sensation. In cases of extreme tissue destruction and trauma,
modulation is an inadequate mechanism for pain control;
therefore, managing pain requires the administration of
exogenous opioids like morphine or hydromorphone.
Processes that act as a warning to ease the response to pain or
inhibit transduction (conversion of a sensory stimulus from
one form to another) or transmission, thereby interrupting or
diminishing the perception of pain, are known as facilitation
and inhibition:

Facilitation is an unconscious act or protective behavior that
serves to warn the individual of tissue injury and to
encourage behaviors such as ght or ight reactions.13,14
For example, when skin inadvertently makes contact with
an extreme heat source, immediately and without thinking,

www.aornjournal.org

March 2015, Volume 101, No. 3

an autonomic response causes rapid or facilitated movement

away from the heat source.

Inhibition is the hypothesis that during periods of threat,
pain is numbed so that it does not compromise function.
The gate theory of pain control proposed by Melzack and
Wall in 1965 suggests that the transmission of information
across the point of contact can be diminished and blocked.2,4
As a result, the perception of the severity of the painful
stimulus is either decreased or not sensed at all. Another way
to explain this is by the activation of a nerve ber that is
associated with a low-threshold sensation such as touch.
Touch stimulates an inhibitory nerve in the spinal cord that
inhibits synaptic transmission, which could possibly explain
why rubbing an injured area helps reduce the sensation of
pain. Another example is a transcutaneous electrical nerve
stimulation (TENS) unit, which sends a low-impulse electrical signal across nerves that interrupts or blocks the signal
going to the brain, decreasing the sensation of pain.
Neuropathic pain consists of injury to or alteration of the normal
sensing and modulating systems.5,9,10 There are many processes
procient at generating neural modications to create neuropathic pain, including atypical nerve redevelopment, amplied
communication of membrane sodium channels, temporary loss
of inhibition on modulating processes, and reduced availability
of m-opioid peptide (MOP) receptors. The MOP receptors are a
group of receptors that bind enkephalins and endorphins. The
typical m receptor agonist (ie, a chemical that binds and activates
a receptor) is morphine, the principal psychoactive substance in
opium; the m refers to morphine. Triggering the m receptor by
morphine causes analgesia, sedation, a minor drop in blood
pressure, urticaria (ie, hives), euphoria, decreased respirations,
miosis (ie, constricted pupils), and reduced bowel motility (from
receptors located in the intestinal tract) that can lead to constipation and can also cause nausea. Some effects (eg, analgesia,
sedation, euphoria, reduced breathing) have a tendency to
decrease over time with continued use as tolerance develops.
Unusual nerve redevelopment may occur after peripheral nerve
injury, leading to the development of a neuroma on the nerve
trunk.15 These nerve sprouts can produce extemporaneous release
of impulses leading to a perception of pain. A good example would
be phantom limb sensations (ie, the perception that an amputated
limb still exists and can experience all the sensations it did when
intact). Phantom limb pain is unpleasant sensations (mild or
extreme pain) in the absent limb.2,4 Approximately 60% to 80%
of people who have experienced a limb amputation report
phantom limb sensations, and the majority report sensations of
pain.16 Currently, the predominant theory for the cause of
phantom pain is irritation in the severed nerve endings (ie,

www.aornjournal.org

Pathophysiology of Pain

neuromas). When a limb is amputated, many severed nerve

endings remain in the stump. Researchers hypothesize that these
nerve endings can become irritated and transmit anomalous
signals to the brain. These anomalous signals may be construed
by the brain as pain. This signal has been termed maladaptive
change because there is a conict between the message being sent
and the message that is received (ie, the signal being sent is not
the signal message that is received).16 Another explanation is that
a nerve, which would have ended in the amputated limb, is
pinched more centrally. The brain recognizes the pain but
accounts for it occurring at the area mapped out for the missing
limb. One therapy that has been successful at minimizing or
eliminating phantom limb pain is to provide chiropractic sessions
to relieve pressure on the nerves leading to the missing limb.
An increased presence of sodium channels within the nerve
bers of damaged nerves is also believed to trigger ectopic
nerve growth after peripheral nerve injury. The amassing of
sodium channels decreases the threshold of stimulation,
expediting the repetitive ring of the injured neurons and
creating the sensation of pain. During an action potential
when sodium moves into the cell and potassium moves out, an
accumulation of sodium channels leaves the doors open so to
speak, and this results (using the earlier example of the subway
train) in the potential traveling faster and irregularly and not
allowing potassium to exit completely, resulting in irregular
pain conduction with differences in intensity.
The loss of impeding mechanisms that are the consequence of
peripheral nerve injury may be caused by hypersensitivity and
pain.17,18 A considerable decrease in gamma aminobutyric
acid (GABA)-mediated inhibition occurs after nerve injury
caused by apoptosis (selective death) of GABAergic neurons or
cells. This decrease leads to a failure to interrupt pain signals,
which results in a decrease in the perceived threshold of pain
and a perceived increase in the pain experience.19,20
Trauma may result in a windup phenomenon that concludes
in a hypersensitivity reaction.21-23 Inammatory cells frame the
areas of tissue injury and generate cytokines and chemokines
that typically regulate the progression of recuperation and tissue
restoration. However, these chemicals also can iname and alter
the properties of the sensory neurons surrounding the area of
injury, creating a sense of pain in areas neighboring those of real
injury. Reduced manifestation of MOP receptors along with
dorsal root ganglions and spinal neurons can contribute to loss
of pain inhibition after peripheral nerve damage.24

THE CLINICAL SCENARIO

Following are clinical examples that illustrate the importance
of the nurse in supporting the patient who is experiencing
AORN Journal j 341

Rodriguez

March 2015, Volume 101, No. 3

Table 1. Nursing Care Plan for a Patient Experiencing Postoperative Pain

Diagnosis

Nursing Interventions

Interim Outcome Statement

Patient demonstrates and/or reports

The patient verbalizes control of
adequate pain control
pain
Patient or designated support

The patient cooperates by lying
person demonstrates knowledge
quietly during intraoperative
of pain management
procedure using block/local
anesthesia

The patients vital signs at discharge
from the OR are equal to or
improved from preoperative values

The patient participates in
management of pain control before
and immediately after surgery

The patient accurately describes the
prescribed regimen for
postoperative pain control at time of
discharge

Acute
Pain

Assesses pain control

Identies cultural and value
components related to pain

Implements pain guidelines

Implements alternative methods
of pain control

Collaborates in initiating patientcontrolled analgesia

Evaluates response to pain
management interventions

Provides pain management
instruction

Includes patient or designated
support persons in perioperative
teaching

Evaluates response to pain
management instruction

Anxiety

Identies psychosocial status

The patient or designated support

Assesses baseline neurological
person verbalizes the sequence of
status
events to expect before and

Identies sensory impairments
immediately after surgery

Identies barriers to communication

Assesses coping mechanisms

Assesses psychosocial issues
specic to the patients medication
management

Identies patient and designated
support persons educational needs

Implements measures to provide
psychological support

Includes patient or designated
support persons in perioperative
teaching

Explains expected sequence of
events

Provides status reports to
designated support person

Evaluates psychosocial response to
plan of care

Evaluates response to instructions

Risk for

Provides care in a nondiscriminatory,
The patient voices satisfaction
Injury
with delivered care
nonprejudicial manner regardless of
the setting in which care is given

Provides care without prejudicial
behavior

Provides care respecting worth and
dignity regardless of diagnosis,
disease process, procedure, or
projected outcome

Maintains patient condentiality

Shares patient information only with
those directly involved in care

Acts as a patient advocate by
protecting the patient from
incompetent, unethical, or illegal
practices

342 j AORN Journal

Outcome Statement

Patient or designated support person

demonstrates knowledge of the
expected psychosocial responses
to the procedure

The patient is the recipient of

competent and ethical care within
legal standards of practice

www.aornjournal.org

March 2015, Volume 101, No. 3

pain. Also included is a care plan for managing pain of the

patient who is experiencing phantom pain.

Pathophysiology of Pain

of gabapentin or pregabalin (an anticonvulsant medication also

used to control or ease nerve pain) in the treatment of the
phantom pain.

Nociceptive Pain
A clinical example of nociceptive pain is illustrated by a
patient who receives conscious sedation without analgesia in
the OR for the incision and drainage of an abscess. The
surgical team place the patient on the OR bed, perform the
surgical prep, and then drape the surgical site. The surgeon
makes an incision directly in the middle of the abscess. At
this point, transduction begins as histamine, bradykinin, and
substance P are released because of the tissue disruption and
cell damage from the incision. An action potential is created
and the transmission of the impulse begins from the area of
injury through the periphery across the synaptic cleft between the nociceptors and the dorsal horn. The impulse
arrives at the spinothalamic tract and ascends to the thalamus, where the perception of pain occurs. At this point, the
patient reacts to the pain because even though they are
sedated, there is no analgesia to prevent the perception of
pain. Because the incision was made in the abscess, which is
an area of inammation, minimal modulation or endogenous
pain control occurs because the noxious stimulus of the
incision is greater than the bodys ability to inhibit the
nociceptive impulse. Here, a local anesthetic such as bupivacaine could be inltrated into the site for a local analgesic effect.

Neuropathic Pain
A clinical example of neuropathic pain is typied by a patient who
undergoes a carpal tunnel release under conscious sedation. After
assessing the patient in the preoperative area, the RN circulator
developed a nursing care plan focused on perioperative pain relief
and prevention (Table 1). Not long after the procedure begins, the
patient, who three years earlier underwent a left below-the-knee
amputation, complains to you of pain at his amputation
site. The RN circulator assesses the site and notes that the
area is clean and dry and the incision is well healed without
drainage or inammation. Based on this assessment, the nurse
determines that the patient is experiencing phantom pain at the
amputation site that may be a result of damaged peripheral
nerves, resulting in the repetitive spontaneous transmission of
pain. The anesthesia professional determines that additional
sedation is required to mute the patients perception of the
phantom limb neuropathic pain. The RN may reposition the
patients extremity for comfort using pillows under the patients
lower extremities to ensure that the patients position is not
causing undue low-back strain that the brain might perceive as
sciatic pain in the amputated limb. The RN may suggest to the
surgeon that the patient may benet from the postoperative use

www.aornjournal.org

CONCLUSION
Although much progress has been made in understanding
and managing pain, pain remains a complex clinical challenge. The OR nurse contributes greatly to managing pain in
patients by understanding the basic pathophysiology of pain.
The scenarios under which hypersensitivity to pain may
occur, such as during a surgical or invasive procedure, can be
eased by proper positioning, use of padding, providing a safe
environment, and minimizing the potential for causing pain.
At the same time, having an understanding of the pain process can assist the nurse to interpret patients self-reports of
pain. Understanding the pathophysiological process of pain
prepares the nurse to support the patient who is experiencing pain.

References
1. Meldrum ML. A capsule history of pain management. JAMA.
2003;290(12):2470-2475.
2. Moayedi M, Davis KD. Theories of pain: from specicity to gate
control. J Neurophysiol. 2013;109(1):5-12.
3. Lautenbacher S, Fillingim RB. Pathophysiology of Pain Perception.
New York, NY: Kluwer Academic/Plenum Publishers; 2004.
4. Kopf A, Patel NB. Guide to Pain Management in Low-Resource
Settings. Seattle, WA: International Association for the Study of
Pain; 2010.
5. McCaffery M, Pasero C. Pain: Clinical Manual. St. Louis, MO:
Mosby; 1999.
6. Layzell M. Current interventions and approaches to postoperative
pain management. Br J Nurs. 2008;17(7):414-419.
7. Kehlet H. Fast-track surgery-an update on physiological care
principles to enhance recovery. Langenbecks Arch Surg. 2011;
396(5):585-590.
8. National Pharmaceutical Council and Joint Commission on
Accreditation of Healthcare Organizations. Pain: Current Understanding of Assessment, Management, and Treatments. Reston, VA:
National Pharmaceutical Council; 2001.
9. Dubin AE, Patapoutian A. Nociceptors: the sensors of the pain
pathway. J Clin Invest. 2010;120(11):3760-3772.
10. Fishman SM, Ballantyne JC, Rathmell JP. Bonicas Management of
Pain. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.
11. Walker JA. Total hip replacement: improving patients quality of
life. Nurs Stand. 2010;24(23):51-57.
12. Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs. 2003;63(7):
649-671.
13. Raj PP. Intervertebral disc: anatomy-physiology-pathophysiologytreatment. Pain Pract. 2008;8(1):18-44.
14. Johnston-Walker E, Hardcastle J. Neurovascular assessment in the
critically ill patient. Nurs Crit Care. 2011;16(4):170-177.

AORN Journal j 343

Rodriguez
15. Rasul ZN, Sell P. Lumbar nerve root pain: what works and what
doesnt? Int Muscul Med. 2009;31(4):166-171.
16. Ramchandran VS, Hirstein W. The perception of phantom limbs.
The D.O. Hebb lecture. Brain. 1998;121(9):1603-1630.
17. Fadl YY, Ellenbogen KA, Grubb RL Jr, Khoo-Summers L,
Lindsay BD. A review of spinal injuries in the invasive cardiologist II:
prevention and treatment. Pacing Clin Electrophysiol. 2007;30(9):
1149-1157.
18. France CR. Decreased pain perception and risk for hypertension:
considering a common physiological mechanism. Psychophysiology. 1999;36(6):683-692.
19. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis,
pathophysiological mechanisms, and treatment. Lancet Neurol.
2010;9(8):807-819.
20. Tracey I, Mantyh PW. The cerebral signature for pain perception
and its modulation. Neuron. 2007;55(3):377-391.
21. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain
mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463-484.

344 j AORN Journal

March 2015, Volume 101, No. 3

22. Mertin S, Sawatzky JA, Diehl-Jones WL, Lee TW. Roadblock to
recovery: the surgical stress response. Dynamics. 2007;18(1):
14-20.
23. Moayedi M, Davis KD. Theories of pain: from specicity to gate
control. J Neurophysiol. 2013;109(1):5-12.
24. Schnitzler A, Ploner M. Neurophysiology and functional neuroanatomy of pain perception. J Clin Neurophysiol. 2000;17(6):
592-603.

Les Rodriguez, MSN, MPH, RN, ACNS-BC,

APRN
is a pain management clinical nurse specialist at AC
Medical Management Clinics, Fort Worth, TX. Mr
Rodriguez has no declared afliation that could be
perceived as posing a potential conict of interest in
the publication of this article.

www.aornjournal.org

Copyright of AORN Journal is the property of Elsevier Inc. and its content may not be copied
or emailed to multiple sites or posted to a listserv without the copyright holder's express
written permission. However, users may print, download, or email articles for individual use.