Long-term intrathecal morphine and bupivacaine upregulate MOR gene expression in lymphocytes

Campana, Gabriele; Sarti, Donatella; Spampinato, Santi; Raffaeli, William

doi:10.1016/j.intimp.2010.06.016

Cited by 33 publications

(40 citation statements)

References 32 publications

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“…Immunosuppression Immunosuppression is a possible concern in patients treated with IT morphine therapy. In a long‐term study, patients with chronic noncancer pain treated with IT morphine (alone or concomitantly with bupivacaine) had significant increases in mu‐opioid receptor levels in lymphocytes after 12 and 24 months of treatment ( p < 0.05); increases were greater with morphine/bupivacaine combination therapy (95). Because increased mu‐opioid receptor levels could result in immunosuppression, IT opioids should be used with care in immunosuppressed patients.…”

mentioning

confidence: 99%

Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

Deer¹,

Prager

Levy

et al. 2012

Neuromodulation: Technology at the Neural Interface

258

353

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mentioning

confidence: 99%

Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

Deer¹,

Prager

Levy

et al. 2012

Neuromodulation: Technology at the Neural Interface

258

353

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“…We could identify only a few studies, which have systematically addressed this question. The findings suggested that CNCP patients in L‐TOT had a lower proportion of NK cells (Campana et al, ) and of CD56 bright NK cells (Tabellini et al, ) compared to CNCP patients without opioid intake or pain‐free healthy controls. The findings also suggested that CNCP patients in L‐TOT had a higher proportion of IL‐2‐activated NK cells (Tabellini et al, ) and a higher concentration of IL‐1β as a response to TLR agonist stimulation compared to controls (Kwok et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Further, the findings suggested that studies with a shorter duration of opioid treatment (from 1 to 3 months) showed no alterations in the immune system (Mueller et al, ; Zin et al, ), whereas treatment for more than 6 months showed an immune alteration (Campana et al, ; Tabellini et al, ). There was no evidence to support differences in total white blood cell count, in the proportion of CD4+, CD8+ or B cells or in the concentration of MIF, IL‐6, IL‐10, IL‐16, IL‐18, complement C3, IgA, IgM, CD40, CD40L, TNFR2, CCL5 or MCP‐1 between CNCP patients in L‐TOT and CNCP patients without opioid intake or pain‐free healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Only two studies analysed the same type of cells. However, these two studies differed regarding methods of analysis (Campana et al, ; Tabellini et al, ). One (Campana et al, ) found a lower proportion of NK cells in CNCP patients in L‐TOT, while the other (Tabellini et al, ) found normal absolute NK cell counts, but did not report their relative proportions.…”

Section: Discussionmentioning

confidence: 99%

“…One study (Campana et al, 2010) found no difference in the proportion of CD4+ and CD8+ T cells between CNCP patients in L-TOT (n = 19) and pain-free healthy controls (n = 10) using flow cytometry (CD4+: L-TOT: 53.30% ± 1.76 vs. Controls: 43.33% ± 1.66; CD8+: L-TOT: 21.67% ± 2.60 vs. Controls: 25.23% ± 1.85; p > .05).…”

Section: T Cellsmentioning

confidence: 99%

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The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

Diasso

Birke

Nielsen

et al. 2019

European Journal of Pain

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Background and objective Opioids have been increasingly prescribed for chronic non‐cancer pain (CNCP). An association between long‐term opioid treatment (L‐TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L‐TOT on the immune system in CNCP patients. Databases and data treatment A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L‐TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed. Results A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full‐text could not be obtained) and one randomized controlled trial (RCT) and five cross‐sectional studies were included and analysed. L‐TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56bright NK cells, a higher absolute number of IL‐2‐activated NK cells and a higher concentration of IL‐1β as a response to toll‐like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies. Conclusions L‐TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L‐TOT on immune system function. Significance This systematic review found indication that long‐term opioid treatment alters the immune system in chronic non‐cancer pain patients. These alterations involved the NK cells and IL‐1β production. However, the level of evidence is weak.

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The Role of Opioid Receptors in Cancer

et al. 2023

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Opioids are one of the most potent drugs for treating moderate to severe pain. Despite irrefutable clinical application in chronic pain management, the long-term use of opioids has been increasingly questioned due to undesired side effects that demand attention. Opioids such as morphine mediate clinically relevant effects primarily through the μ-opioid receptor that go beyond their classical role as analgesics, causing potentially fatal side effects such as tolerance, dependence, and addiction. Furthermore, there is growing evidence that opioids affect immune system function, cancer progression, metastasis, and recurrence. Though a biological plausibility, the clinical evidence for the action of opioids on cancer is mixed, revealing a more complex picture as researchers struggle to establish a vital link between opioid receptor agonists, cancer progression, and suppression, or both. Thus, in light of the uncertainty of opioid effects on cancer, in this review, a focused overview of the role of opioid receptors in modulating cancer progression, their underlying signaling mechanisms, and the biological activity of opioid receptor agonists and antagonists is provided.

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Long-term intrathecal morphine and bupivacaine upregulate MOR gene expression in lymphocytes

Cited by 33 publications

References 32 publications

Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

The Role of Opioid Receptors in Cancer

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