Opioid Tolerance and Hyperalgesia in Chronic Pain Patients After One Month of Oral Morphine Therapy: A Preliminary Prospective Study

Chu, Larry F.; Clark, David J.; Angst, Martin S.

doi:10.1016/j.jpain.2005.08.001

Cited by 367 publications

(271 citation statements)

References 31 publications

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“…This is in agreement with a number of previous studies reporting the development of hypersensitivity following morphine treatment in rodents Liang et al, 2008;Liang et al, 2011;Muscoli et al, 2010;Vera-Portocarrero et al, 2007). Sensory sensitization induced by opioids has also been reported in clinical studies showing an increase in mechanical sensitivity after repeated exposure to morphine (Chu et al, 2006;Hay et al, 2009). The fact that our morphine treatment procedure did not elicit an increase in heat sensitivity is consistent with other reports suggesting that opioids can sensitize the nociceptive pathways activated by mechanical stimuli to a greater extent than those activated by heat stimuli Cabañero et al, 2009).…”

Section: Discussionsupporting

confidence: 92%

Pain after Discontinuation of Morphine Treatment Is Associated with Synaptic Increase of GluA4-Containing AMPAR in the Dorsal Horn of the Spinal Cord

Cabañero

Baker

Zhou

et al. 2013

Neuropsychopharmacol

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Withdrawal from prescribed opioids results in increased pain sensitivity, which prolongs the treatment. This pain sensitivity is attributed to neuroplastic changes that converge at the spinal cord dorsal horn. We have recently reported that repeated morphine administration triggers an insertion of GluA2-lacking (Ca 2 þ -permeable) a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) in the hippocampus. This finding together with the reported involvement of AMPAR in the mechanisms underlying inflammatory pain led us to hypothesize a role for spinal AMPAR in opioid-induced pain behavior. Mice treated with escalating doses of morphine showed hypersensitivity to mechanical stimulation. Intrathecal administration of a Ca 2 þ -permeable AMPAR selective blocker disrupted morphine-induced mechanical sensitivity. Analysis of the expression and phosphorylation levels of AMPAR subunits (GluA1/2/3/4) in homogenates and in postsynaptic density fractions from spinal cord dorsal horns showed an increase in GluA4 expression and phosphorylation in the postsynaptic density after morphine. Co-immunoprecipitation analyses suggested an increase in GluA4 homomers (Ca 2 þ -permeable AMPAR) and immunohistochemical staining localized the increase in GluA4 levels in laminae III-V. The excitatory postsynaptic currents (EPSCs) recorded in laminae III-V showed enhanced sensitivity to Ca 2 þ -permeable AMPAR blockers in morphinetreated mice. Furthermore, current-voltage relationships of AMPAR-mediated EPSCs showed that rectification index (an indicator of Ca 2 þ -permeable AMPAR contribution) is increased in morphine-treated but not in saline-treated mice. These effects could be reversed by infusion of GluA4 antibody through patch pipette. This is the first direct evidence for a role of GluA4-containing AMPAR in morphineinduced pain and highlights spinal GluA4-containing AMPAR as targets to prevent the morphine-induced pain sensitivity.

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Section: Discussionsupporting

confidence: 92%

Pain after Discontinuation of Morphine Treatment Is Associated with Synaptic Increase of GluA4-Containing AMPAR in the Dorsal Horn of the Spinal Cord

Cabañero

Baker

Zhou

et al. 2013

Neuropsychopharmacol

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“…This was based on the findings of Chu et al that opioid hyperalgesia may develop in as little as four weeks of daily opioid use [16,17]. Narcotic dose and usage was collected and verified through clinic charts, in-patient hospital medication administration records, prescription documentation, and phone interviews.…”

Section: Methodsmentioning

confidence: 99%

Opioid use prior to total hip arthroplasty leads to worse clinical outcomes

Pivec

Issa

Naziri

et al. 2014

International Orthopaedics (SICOT)

182

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Purpose The purpose of this study was to compare the clinical outcomes of patients undergoing total hip arthroplasty (THA) who had been using narcotic medications prior to surgery to those who had not used them. Methods Fifty-four patients (62 hips) who had required opioid analgesia for hip pain in the three months prior to THA were compared to a matched group of opioid-naïve patients. Narcotic consumption was converted to a standardized morphine equivalent dose and compared between both groups of patients during their hospital stay, after six weeks, and at final follow-up. Other outcome measures included clinical outcome scores and the proportion of patients remaining on narcotic pain medication at final follow-up. Results The narcotic group required significantly higher total daily opioid doses as inpatients had a longer hospital stay and a higher proportion of patients who remained on opioids at six weeks and at final follow-up. Of the patients who were taking opioids pre-operatively, 81 % were able to wean off opioids at final follow-up. At a mean post-operative follow-up of 58 months (range, 24-258 months), Harris hip scores were lower in the narcotic group, with a mean of 84 compared to 91 points in the matching group. However, in both cohorts, there were significant improvements in Harris hip scores compared to pre-operative outcomes.

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“…While the early OIH clinical literature was largely anecdotal, several recent cross-sectional quantitative sensory testing (QST) studies have revealed that individuals taking either morphine or methadone are hyperalgesic relative to controls [15], and that opioidmaintained chronic pain patients showed reduced heat pain thresholds and enhanced temporal summation of pain relative to both controls and matched non-opioid chronic pain patients [16]. Some prospective work has been done as well, with some trials observing OIH [17,18] and some not reporting significant changes in pain responses [19].…”

Section: Introductionmentioning

confidence: 99%

Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect

Edwards¹,

Dolman²,

Michna³

et al. 2016

Pain Med

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Objective. Opioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioidinduced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation.Design. The six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment.Setting. A chronic pain management center.Patients. The 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA).Results. In the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:86172). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group.Conclusions. These results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic

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Opioid Tolerance and Hyperalgesia in Chronic Pain Patients After One Month of Oral Morphine Therapy: A Preliminary Prospective Study

Cited by 367 publications

References 31 publications

Pain after Discontinuation of Morphine Treatment Is Associated with Synaptic Increase of GluA4-Containing AMPAR in the Dorsal Horn of the Spinal Cord

Pain after Discontinuation of Morphine Treatment Is Associated with Synaptic Increase of GluA4-Containing AMPAR in the Dorsal Horn of the Spinal Cord

Opioid use prior to total hip arthroplasty leads to worse clinical outcomes

Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect

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