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Patient/Surgical Risk Factors for Chronic Pain and Opioid Dependency 43
benefits associated with antidepressant administration and additional future studies
should seek to replicate these findings [53].
Anticonvulsants (Gabapentinoids)
Gabapentinoids such as gabapentin and pregabalin are commonly used in treatment of
CPSP as there is frequently a neuropathic component [28]. Gabapentinoids bind to the
ɑ-2δ subunit of presynaptic voltage-gated calcium channels which blocks the release
of excitatory neurotransmitters from activating pain-transmitting neurons [54]. A
study conducted on patients who underwent single-level lumbar discectomy showed
that patients who received gabapentin 300 mg had significantly lower VAS score at all
time points and they consumed less fentanyl. Patients who received gabapentin 600,
900, 1200 mg had lower VAS scores at all the time points than patients who received
gabapentin 300 mg [55]. Other recent studies have demonstrated that gabapentinoids
may have minimal effect on length of postoperative pain but are associated with a
decreased duration of postoperative opioid use [18]. Additional studies are needed
to determine the appropriate use of gabapentinoids as a CPSP prevention modality
[18].
5 Opioid Dependence and OUD Background
OUD is a treatable disease that affects nearly 16 million patients worldwide and
over 6 million Americans [56, 57]. OUD is defined as a problematic use of opioids
resulting in clinically significant distress or impairment [58]. The diagnosis spans a
continuum from mild, moderate, to severe including opioid dependence in the mild
subset and addiction in the severe subset [58].
The following criteria are required for diagnosis of OUD.
1. Opioid are taken in larger amounts or over a longer period of time than was
intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid
use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the
opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfill major role obligations at
work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interper-
sonal problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced
because of opioid use.
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44 W. Carter et al.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recur-
rent physical or psychological problem that is likely to have been caused or
exacerbated by the substance.
10. Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication
or desired effect.
b. A markedly diminished effect with continued use of the same amount of an
opioid.
Note: This criterion is not considered to be met for those taking opioids solely
under appropriate medical supervision.
11. Withdrawal, as manifested by either of the following:
a. The characteristic opioid withdrawal syndrome (refer to Criteria A and B
of the criteria set for opioid withdrawal, pp. 547–548).
b. Opioids (or a closely related substance) are taken to relieve or avoid
withdrawal symptoms.
Note: This criterion is not considered to be met for those individuals taking opioids
solely under appropriate medical supervision.
Opioid use disorder can be classified by severity according to the number of criteria
met: Mild (2–3 criteria); Moderate (4–5 criteria); Severe (6 or greater criteria). Note:
Criteria from American Psychiatric Association (2013). Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition. Washington, DC, American Psychiatric
Association page 541 [58].
OUD does not discriminate, impacting all races, ethnicities, and economic groups
[59]. While OUD is similar to other substance use disorders, it is unique in the
short lead time (4–8 weeks) to physical dependence [60]. The intrinsic properties of
opioid receptors and downward impact on dopamine pathways, leads to higher levels
of positive reinforcement than most other substances. Additionally, the negative
symptoms of opioid withdrawal, including chills, diaphoresis, nausea and vomiting,
and intense cravings further reinforce the need to continue opioid use [60].
6 Opioid Dependence Risk Factors
While persistent opioid use after surgery may be the result of continued postoper-
ative surgical pain, it may also represent non-pain etiologies including emotional
suffering, the development of opioid dependence, or the development of an OUD.
Some studies suggest persistent use of opioids following TKA despite improvement
in joint pain suggesting the possible development of misuse [10]. The etiology for
opioid dependence and OUD is multifactorial, including both genetic, psychologic,
pharmacologic, and environmental factors.
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Patient/Surgical Risk Factors for Chronic Pain and Opioid Dependency 45
Risk factors for the development of persistent post-surgical opioid use include
younger age, sleep disturbance, tobacco use, history of past opioid use (including
remote), mood disorders, history of chronic pain, and history of a substance use
disorder [14].
Exposure to opioids is also a known pharmacological risk factor. Even short expo-
sure to opioids has been associated with tolerance and hyperalgesia. High intraoper-
ative doses of opioids have been found to contribute to higher levels of postoperative
pain and higher amounts of morphine milliequivalents (MME) [61–64]. Each day
of prescription opioid use can increase the risk of LTOT, with chronic opioid use
occurring in as little as 5 days [64] in opioid naive patients [15].
Preoperative Assessment
All patients should be screened for OUD preoperatively. Early identification of
patients with OUD can enable improved coordination of care and patient education.
Validated screening tools include National Institutes on Drug Abuse (NIDA) quick
screen, Drug Abuse Screening Tool (DAST-10), and Screening, Brief Interventions,
Referral to Treatment (SBIRT) [65]. Additionally, obtaining a personal or family
history of OUD, SUD, or untreated mental illness is advised [65, 66]. Furthermore,
attention to signs of withdrawal, including nausea/vomiting, diarrhea, lacrimation,
rhinorrhea, diaphoresis, shivering, piloerection, yawning, sneezing, restlessness, and
tremor are warranted [67]. When assessing a patient for OUD, it is important to use
non-stigmatizing language and to set realistic expectations for pain control.
7 Opioid Dependence Prevention
Despite the development of minimally invasive surgeries and new non-opioid medi-
cations, 80% of patients worldwide who undergo surgery receive opioids for postop-
erative pain relief [68]. Therefore, the reduction of opioid overuse is of utmost impor-
tance. During the perioperative period it is important to minimize opioids while also
providing adequate analgesia. This can be accomplished in a variety of ways. One
way is using multimodal analgesics; a regimen consisting of opioid, non-opioid medi-
cations and nonpharmacologic methods should be employed. A combination of anti-
inflammatory (NSAID), gabapentin, acetaminophen, dexmedetomidine, and weak
opioids can provide adequate analgesia without significant adverse effects [68]. The
use of Enhanced Recovery after Surgery (ERAS) protocols are essential to creating
multimodal analgesia regiments. One study of more than 600 patients managed with
an ERAS protocol showed a 72% reduction in median opioid consumption and 16%
of these patients were opioid-free from admission to the third postoperative day
[69]. When appropriate, neuraxial or regional anesthesia techniques can be used
for pain control to further decrease opioid use. Multiple studies have demonstrated
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46 W. Carter et al.
the significant benefits of using regional anesthesia for various surgical procedures
including total knee arthroplasty, hepatectomy, colectomy [68]. Furthermore, it is
also recommended to discharge patients on a multimodal analgesic regimen with the
minimal amount of opiates needed to decrease overall opiate use and opiate-related
side effects [70].
8 OUD/Treatment
Multifactorial care is the mainstay of OUD treatment, including behavioral and
pharmacological therapies. Nonpharmacological therapies to treat OUD include:
cognitive behavioral therapy (CBT), contingency management, and group therapy.
Currently, there are 3 Federal Drug Administration medications, methadone,
buprenorphine, and naltrexone, for the treatment of OUD (MOUD). MOUD has
been found to improve outcomes, decrease morbidity and mortality, and increase
retention in treatment [71]. Despite the evidence for MOUD, access to these medi-
cations continues to be limited [72]. The pharmacologic profiles and dosing for all
three MOUD differ and are reviewed in Table 1. Prior to 2023, it was required that
physicians prescribing suboxone for OUD obtain an X-waiver, however with the
passage of the 2023 Consolidated Appropriations Act (P.L. 117–328) [73], signed
into law on Dec. 29, 2022, the requirement has since been lifted. The act amended the
Controlled Substances Act to eliminate the requirement for qualified practitioners to
first obtain a special x waiver to prescribe medications such as BUP for the treatment
of opioid use disorder (OUD).
It is important for patients currently prescribed MOUD and scheduled for
upcoming surgery be evaluated preoperatively. Part of the preoperative assessment
includes coordinating care between the surgical, anesthesiology, and outpatient treat-
ment teams as well as with the patient. If the patient is prescribed either a full
mu-agonist (methadone) or partial mu-agonist (buprenorphine) it is recommended
to continue these medications during the perioperative period [67]. Unlike full mu-
agonist or partial mu-agonist, which are routinely continued perioperatively, patients
prescribed mu-antagonist (naltrexone) need to have the medication discontinued prior
to surgery when opioids are anticipated to be needed. If patients receive monthly
injectable naltrexone, XR-NXT, it is recommended elective surgery be delayed
28 days following the last administration [74]. Oral naltrexone is recommended
to be discontinued 48–72 hour prior to surgery [75]. Regardless of what the patient is
prescribed for OUD, it is encouraged that the perioperative plan is individualized to
the patient and multimodal analgesics are employed during the perioperative period;
opioids, non-opioid medications and nonpharmacologic methods.
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Patient/Surgical Risk Factors for Chronic Pain and Opioid Dependency 47
Table 1 Comparison of the 3 FDA-approved medications for OUD treatment [66]
Methadone Buprenorphine Naltrexone
Mechanism of action Full agonist at
mu-opioid receptor
Partial agonist at
mu-opioid receptor
Antagonist at
mu-opioid receptor
Dosing average range • 80–100 mg PO daily • 4–24 mg SL/PO
daily
• 380 mg IM Depot
injection
• 50 mg PO daily
Setting • Licensed outpatient
treatment program
(OTP)
• Any medical setting
• X-waiver no longer
required as of 2023
• Any medical setting
Advantages • Care provided in
highly structured
supervised setting
with built in
resources
• Use in co-morbid
pain management
•Lowdiversion
• Care provided in a
variety of outpatient
models; less
structured then OTP
•Lowerriskof
overdose
• Use in co-morbid
pain management
• Dosing flexibility
•Lowdiversion
• Not an opioid
• Improved
compliance
• No physical
dependence
• Verifiable dosing
• Less stigma
Disadvantages • Caution with QTc
prolongation
• Adverse Effects:
May increase LFTs,
constipation and
other opioid-related
side effects
• Caution with
increased overdose
risk
• Withdrawal with
abrupt cessation
• Diversion possible
• Adverse Effects:
Constipation and
other opioid-related
side effects
• Withdrawal with
abrupt cessation
• Cannot be used for
comorbid pain
management
• Adverse Effects: Flu
like symptoms at
first injection
• Requires ~10-day
opioid free period
prior to initiation to
avoid precipitated
withdrawal
9 Conclusion
CPSP and opioid dependence continues to be an issue affecting patients following
surgery. Although the mechanism behind CPSP development is not fully understood,
it is important to employ multimodal analgesics; opioids, non-opioid medications and
nonpharmacologic methods, when applicable. Prior to surgery, all patients should
be screened for opioid use disorder as there are additional analgesic techniques and
medications that can be used throughout the perioperative period to further benefit
these patients.
Key Takeaways
1. CPSP is pain that develops or increases in intensity after a surgical procedure or
injury and persists for at least 3 months following the surgery and typical healing
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48 W. Carter et al.
process. Prevention of CPSP can vary from using minimally invasive surgical
technique, utilizing local/regional anesthetics, and ketamine IV treatments.
2. Limiting opioid prescribing may help to decrease the risk of long-term opioid
use as well as t he development of OUD.
3. It is encouraged that the perioperative analgesic plan is individualized to the
patient and that multimodal analgesics are employed during the perioperative
period; opioids, non-opioid medications as well as nonpharmacologic methods.
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