Anagelsic effect of intracerebroventricular (ICV) somatostatin-14 (SOM-14), arginine vasopressin (AVP) and oxytocin (OT) in a patient with terminal cancer pain

Madrazo, Ignacio; Franco-Bourland, Rebecca E.; León, Verónica; Mena, Iván X.

doi:10.1016/0304-3959(87)91355-8

Cited by 4 publications

(2 citation statements)

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“…1 In contrast, direct administration of oxytocin into cerebrospinal fluid produced analgesia in a patient with cancer pain. 2 In animals, activation of oxytocin fibers descending from the paraventricular nucleus to the spinal cord participates in stress induced analgesia 3 and reduces hypersensitivity after injury. 4 Additionally, we recently showed that pain and hypersensitivity following surgery recovers more quickly in animals and humans when the surgery occurs near the time of delivery, and that this is reversed by spinal injection of an oxytocin receptor-preferring antagonist.…”

Section: Introductionmentioning

confidence: 99%

Phase 1 Safety Assessment of Intrathecal Oxytocin

2015

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Background Preclinical data suggest that oxytocin reduces hypersensitivity by actions in the spinal cord, but whether it produces antinociception to acute stimuli is unclear. Here we examined the safety of intrathecal oxytocin and screen its effects on acute noxious stimuli. Methods Following institutional review board and Food and Drug Administration approval, healthy adult volunteers received 5, 15, 50, or 150 µg intrathecal oxytocin in a dose escalating manner in cohorts of 5 subjects. Hemodynamic and neurologic assessments were performed for 4 hour following injections and 24 hr later, at which time serum sodium was also measured. Cerebrospinal fluid was obtained 60 min after injection, and responses to noxious heat stimuli in arm and leg as well as temporal summation to repeated application of a von Frey filament were obtained. Results One subject receiving the highest dose experienced transient hypotension and bradycardia as well as subjective numbness in a lumbo-sacral distribution. No other subject experienced subjective or objective neurologic symptoms. Overall, blood pressure and heart rate increased 1–4 hr after injection by < 15%, with no dose dependency. There was no effect on serum sodium and cerebrospinal fluid oxytocin increased in a dose-dependent manner after injection. Pain scores to noxious heat stimuli were unaffected by oxytocin, and the temporal summation protocol failed to show summation before or after drug treatment. Conclusions This small study supports further investigation of oxytocin for analgesia for hypersensitivity states, with continued systematic surveillance for possible effects on blood pressure, heart rate, and neurologic function.

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Section: Introductionmentioning

confidence: 99%

Phase 1 Safety Assessment of Intrathecal Oxytocin

2015

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“…Various rodent pain models have also revealed that exogenous OXT and AVP can alleviate pain‐related behaviour 7,9‐15 . Furthermore, clinical studies have reported that OXT and AVP are effective in alleviating pain in humans 16‐20 . Considering that OXT and AVP have been shown to exert analgesic effects in patients with back pain and other pain related to orthopedic disease, 18,20 they may also prove to be effective candidates for a novel conservative OA treatment option.…”

Section: Introductionmentioning

confidence: 99%

The neurohypophysial oxytocin and arginine vasopressin system is activated in a knee osteoarthritis rat model

Nishimura

Kawasaki

Suzuki

et al. 2020

J Neuroendocrinology

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Osteoarthritis (OA) causes chronic joint pain and significantly impacts daily activities. Hence, developing novel treatment options for OA has become an increasingly important area of research. Recently, studies have reported that exogenous, as well as endogenous, hypothalamic‐neurohypophysial hormones, oxytocin (OXT) and arginine‐vasopressin (AVP), significantly contribute to nociception modulation. Moreover, the parvocellular OXT neurone (parvOXT) extends its projection to the superficial spinal dorsal horn, where it controls the transmission of nociceptive signals. Meanwhile, AVP produced in the magnocellular AVP neurone (magnAVP) is released into the systemic circulation where it contributes to pain management at peripheral sites. The parvocellular AVP neurone (parvAVP), as well as corticotrophin‐releasing hormone (CRH), suppresses inflammation via activation of the hypothalamic‐pituitary adrenal (HPA) axis. Previously, we confirmed that the OXT/AVP system is activated in rat models of pain. However, the roles of endogenous hypothalamic‐neurohypophysial hormones in OA have not yet been characterised. In the present study, we investigated whether the OXT/AVP system is activated in a knee OA rat model. Our results show that putative parvOXT is activated and the amount of OXT‐monomeric red fluorescent protein 1 positive granules in the ipsilateral superficial spinal dorsal horn increases in the knee OA rat. Furthermore, both magnAVP and parvAVP are activated, concurrent with HPA axis activation, predominantly modulated by AVP, and not CRH. The OXT/AVP system in OA rats was similar to that in systemic inflammation models, including adjuvant arthritis; however, magnocellular OXT neurones (magnOXT) were not activated in OA. Hence, localised chronic pain conditions, such as knee OA, activate the OXT/AVP system without impacting magnOXT.

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Substance P-like immunoreactivity and somatostatin-like immunoreactivity in the ventricular fluid of patients with chronic pain syndromes

Jost

Reuner

Geiger

et al. 1991

Eur Arch Psychiatry Clin Nuerosci

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Substance P-like and somatostatin-like immunoreactivities (SPLI and SLI) were determined in ventricular fluid of patients with chronic pain syndromes and in a comparison group with multiple sclerosis, essential tremor, epilepsy and postanoxic myoclonus. Concentrations of SPLI and SLI were non-significantly decreased by 40% and 33% in chronic pain patients as compared with control patients without pain. There were no differences apparent between subgroups of pain patients (deafferentation pain, neoplasia-induced pain, thalamic pain). High pressure liquid chromatography combined with radioimmunoassay showed marked heterogeneity of SPLI and SLI.

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Anagelsic effect of intracerebroventricular (ICV) somatostatin-14 (SOM-14), arginine vasopressin (AVP) and oxytocin (OT) in a patient with terminal cancer pain

Cited by 4 publications

References 0 publications

Phase 1 Safety Assessment of Intrathecal Oxytocin

Phase 1 Safety Assessment of Intrathecal Oxytocin

The neurohypophysial oxytocin and arginine vasopressin system is activated in a knee osteoarthritis rat model

Substance P-like immunoreactivity and somatostatin-like immunoreactivity in the ventricular fluid of patients with chronic pain syndromes

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