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The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid-like receptor ORL-1 and is thought to be involved in pain transmission and modulation. Human studies have not yet defined its role in pain patients. The aims of this study were 1) to verify the presence of N/OFQ in the cerebrospinal fluid (CSF) of human controls and patients with chronic noncancer pain, including those treated with intrathecally administered morphine, and 2) to determine whether pain or treatment with long-term intrathecal morphine influences its levels. The CSF of 27 patients (nine controls and 18 with chronic noncancer pain, of whom 12 were treated chronically with intrathecally administered morphine and six were opioid naïve) was analyzed, blindly, with radioimmunoassay methods. N/OFQ was detected in all patients. Mean CSF concentrations were lowest in the morphine-treated group and highest in the untreated chronic pain patients (12.06+/-1.19 and 57.41+/-10.06 fmol/ml, respectively), and the difference between the morphine-treated group and controls was statistically significant (44.72+/-13.56 fmol/ml, P<0.05). The presence of N/OFQ peptide in human CSF may correlate with biological activities that are influenced by different pain states and long-term intrathecal-morphine treatment. Further studies should verify whether the determination of this peptide CSF level may provide information on opioid treatment efficacy and on the presence of opioid tolerance.

Objectives: To assess the efficacy and the safety of our rapid detoxification protocol in preventing signs and symptoms of withdrawal and pain severity.Design: Prospective, open-label case series study.Settings: Public primary care at the Pain and Palliative Care Unit of the Infermi Hospital of Rimini, Italy.Patients: The authors studied 10 consecutive patients suffering from chronic noncancer pain who were refractory to intrathecal (IT) morphine, and hence indicated for ziconotide therapy.Interventions: IT pump was refilled with saline solution, and each patient received endovenous morphine, oral clonidine, ketoprofen, and lorazepam for the first 3 days, and slow-release tramadol, oral clonidine, and ketoprofen for 10 days. Ziconotide therapy was started at the end of the 2-week detoxification treatment.Main outcome measures: The observer-rated opioid withdrawal scale (OOWS) was used for the assessment of withdrawal signs, visual analogue scale was used for pain intensity assessment, and also adverse events were recorded.Results: Withdrawal symptoms were experienced by 3 patients (30 percent). Their average OOWS decreased significantly (p 0.05) from 4.3 ± 2.5 to 1.7 ± 0.6 at days 3 and 14 of protocol, respectively, with no increment of pain intensity. Withdrawal symptoms were resolved in 4 days on average without the need of adjuvant medications. One patient with high morphine dosage (20 mg/d), interestingly, did not show any withdrawal symptoms.Conclusions: The detoxification protocol was effective in preventing withdrawal signs without increasing pain severity, allowing to rapidly convert IT morphine to ziconotide monotherapy in patients who are refractory to morphine.

Background: The influence of long‐term opioid administration on hormonal levels is not well characterized in the literature. We previously showed that intrathecal opioid therapy significantly influences the homeostasis of immune and endocrine systems. Other authors confirmed that exogenous and endogenous opioids induce this effect. They have a cytokine‐like behavior and may function as neurotransmitters, neuromodulators or hormones, as concerning their synthesis, storage and release. Aims: To assess the effects of morphine long‐term intrathecal administration on serum levels of Gonadal, Thyroidal and Adrenal axis hormones in an elderly population affected by chronic pain; to assess the correlation between hormone levels and morphine dosage. Methods: Patients suffering from chronic non‐cancer pain with or without intrathecal drug delivery system were studied and hormonal levels were monitored, using an immunoradiometric assay kit. Results: The long‐term administration of intrathecal morphine influenced part of the endocrine system, in particular, there was a reduction of FSH and LH and an increment of GH serum levels; this effect was morphine dose dependent. Conclusion: Long‐term intrathecal opioid administration influenced FSH, LH and GH serum levels. Data on this issue are inadequately described in the literature. The finding of endocrine effects of opioid therapy, nonetheless, cannot be ignored, as it may have clinical relevance in both elderly and young population. We believe that during long intrathecal pain treatments with morphine, clinicians should be aware of both immediate and later opioids side effects, and in particular, they should monitor immune and endocrine changes.