Naloxone and Maintenance Naltrexone as Novel and Effective Therapies for Immunotherapy-Induced Pruritus: A Case Report and Brief Literature Review

Singh, Raj; Patel, Purvi; Thakker, Malvi; Sharma, P.; Barnes, Martin; Montana, Steven

doi:10.1200/jop.18.00797

Cited by 9 publications

(6 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Naltrexone is an effective treatment for reducing uremic pruritus in patients with chronic kidney disease (Peer et al, 1996;Legroux-Crespel et al, 2004). Furthermore, case reports have shown that naloxone and naltrexone are effective therapies for anti-PD1 immunotherapy-induced pruritus (Kwatra et al, 2018;Singh et al, 2019). Although MOR antagonists have shown some benefits for treating pruritus in these pathological conditions, the specific cellular targets of MOR antagonists for treating chronic itch remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with chronic itch commonly experience high sensitivity to pruritogens, mechanically evoked itch sensations, and spontaneous itch (Ikoma et al, 2006;LaMotte et al, 2014). Opioid receptor antagonists (e.g., naloxone, naltrexone, and nalbuphine) have shown to be effective for chronic itch following dermatitis, uremic pruritus, and anti-PD1 immunotherapy induced itch (Brune et al, 2004;Kwatra et al, 2018;Reszke and Szepietowski, 2018;Serrano et al, 2018;Kremer, 2019;Singh et al, 2019). However, we know little about the molecular mechanisms underlying opioid-induced itch beyond a demonstrated interaction between µ-opioid receptor isoform 1D (MOR1D) and gastrin-releasing peptide receptor (GRPR) (Liu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition

Wang

Jiang

Yao

et al. 2020

Brain

View full text Add to dashboard Cite

Opioids such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Recent progress has advanced our understanding of itch circuits in the spinal cord. However, the mechanisms underlying opioid-induced itch are not fully understood, although an interaction between µ-opioid receptor (MOR) and gastrin-releasing peptide receptor (GRPR) in spinal GRPR-expressing neurons has been implicated. In this study we investigated the cellular mechanisms of intrathecal opioid-induced itch by conditional deletion of MOR-encoding Oprm1 in distinct populations of interneurons and sensory neurons. We found that intrathecal injection of the MOR agonists morphine or DAMGO elicited dose-dependent scratching as well as licking and biting, but this pruritus was totally abolished in mice with a specific Oprm1 deletion in Vgat+ neurons [Oprm1-Vgat (Slc32a1)]. Loss of MOR in somatostatin+ interneurons and TRPV1+ sensory neurons did not affect morphine-induced itch but impaired morphine-induced antinociception. In situ hybridization revealed Oprm1 expression in 30% of inhibitory and 20% of excitatory interneurons in the spinal dorsal horn. Whole-cell recordings from spinal cord slices showed that DAMGO induced outward currents in 9 of 19 Vgat+ interneurons examined. Morphine also inhibited action potentials in Vgat+ interneurons. Furthermore, morphine suppressed evoked inhibitory postsynaptic currents in postsynaptic Vgat− excitatory neurons, suggesting a mechanism of disinhibition by MOR agonists. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of bombesin-saporin, whereas intrathecal GRP-induced itch response remained intact in mice lacking Oprm1-Vgat. Intrathecal bombesin-saporin treatment reduced the number of GRPR+ neurons by 97% in the lumber spinal cord and 91% in the cervical spinal cord, without changing the number of Oprm1+ neurons. Additionally, chronic itch from DNFB-induced allergic contact dermatitis was decreased by Oprm1-Vgat deletion. Finally, naloxone, but not peripherally restricted naloxone methiodide, inhibited chronic itch in the DNFB model and the CTCL model, indicating a contribution of central MOR signalling to chronic itch. Our findings demonstrate that intrathecal morphine elicits itch via acting on MOR on spinal inhibitory interneurons, leading to disinhibition of the spinal itch circuit. Our data have also provided mechanistic insights into the current treatment of chronic itch with opioid receptor antagonist such as naloxone.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition

Wang

Jiang

Yao

et al. 2020

Brain

View full text Add to dashboard Cite

show abstract

“…12 The efficacy of oral naltrexone has been documented in patients with pruritus asso-FIGURE Literature Review Search Results ciated with immune checkpoint inhibitors, psoriasis, eczema, lichen simplex chronicus, prurigo nodularis, cholestasis, uremia, and multiple rheumatologic diseases. 3,4,[7][8][9][12][13][14] Opioid pathways also may be involved in peripheral and/or central processing of pruritus associated with PV.…”

Section: Discussionmentioning

confidence: 99%

Naltrexone: a Novel Approach to Pruritus in Polycythemia Vera

Nikzad

2023

Federal Practitioner

View full text Add to dashboard Cite

Background: Pruritus is a characteristic and often debilitating clinical manifestation reported by about 50% of patients with polycythemia vera (PV). Interventions for PV-associated pruritus include phlebotomy, antidepressants, antihistamines, phototherapy, interferon a, myelosuppression, and signaling pathway-specific agents. Case Presentation: A 40-year-old man presented with Janus kinase 2 (Jak2)-positive PV complicated by intractable pruritus that was not alleviated by multimodal therapy and lifestyle modifications. Following the initiation of naltrexone, the patient experienced immediate relief that has persisted for 2 years. Conclusions: This case demonstrates a novel approach to the management of PV-associated pruritus. Notably, naltrexone is an affordable, accessible, and potentially effective option for patients with intractable PV pruritus. Future directions involve consideration of case series or randomized clinical trials investigating the efficacy and pathophysiology of naltrexone in treating PV-associated pruritus.

show abstract

“…Moreover, OT-induced grooming and scratching behavior can be blocked by an opiate receptor antagonist, naloxone ( Van Wimersma Greidanus et al, 1990 ). Opioid receptor antagonists was also shown to reduce scratching following dermatitis, uremic pruritus, and anti-PD1 immunotherapy ( Brune et al, 2004 ; Kwatra et al, 2018 ; Reszke and Szepietowski, 2018 ; Serrano et al, 2018 ; Singh et al, 2019 ). This reduction in scratching is thought to reflect a relief of itch sensation, because opiate antagonists reduced experimental itch sensation in humans ( Heyer et al, 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

Guo

Matsuda

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Oxytocin (OT), a neuropeptide involved in the regulation of complex social and sexual behavior in mammals, has been proposed as a treatment for a number of psychiatric disorders including pain. It has been well documented that central administration of OT elicits strong scratching and grooming behaviors in rodents. However, these behaviors were only described as symptoms, few studies have investigated their underlying neural mechanisms. Thus, we readdressed this question and undertook an analysis of spinal circuits underlying OT-induced scratching behavior in the present study. We demonstrated that intrathecal OT induced robust but transient hindpaw scratching behaviors by activating spinal OT receptors (OTRs). Combining the pre-clinical and clinical evidence, we speculated that OT-induced scratching may be an itch symptom. Further RNAscope studies revealed that near 80% spinal GRP neurons expressed OTRs. OT activated the expression of c-fos mRNA in spinal GRP neurons. Chemical ablation of GRPR neurons significantly reduced intrathecal OT-induced scratching behaviors. Given GRP/GRPR pathway plays an important role in spinal itch transmission, we proposed that OT binds to the OTRs expressed on the GRP neurons, and activates GRP/GRPR pathway to trigger itch-scratching behaviors in mice. These findings provide novel evidence relevant for advancing understanding of OT-induced behavioral changes, which will be important for the development of OT-based drugs to treat a variety of psychiatric disorders.

show abstract

Naloxone and Maintenance Naltrexone as Novel and Effective Therapies for Immunotherapy-Induced Pruritus: A Case Report and Brief Literature Review

Cited by 9 publications

References 5 publications

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition

Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition

Naltrexone: a Novel Approach to Pruritus in Polycythemia Vera

Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System

Contact Info

Product

Resources

About