Substance P and calcitonin gene related peptide mediate pain in chronic pancreatitis and their expression is driven by nerve growth factor.
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CONTEXT: Calcitonin gene-related peptide (CGRP), substance P and nerve growth factor play an important role in inflammatory pain in various somatic pain models but their role in chronic pancreatitis has not been well studied. OBJECTIVES: The aim of this study was to investigate the effects of intrathecal administration of calcitonin gene-related peptide antagonist and substance P receptor antagonist on pain behavior in a rat model of chronic pancreatitis and to determine whether nerve growth factor drives the up-regulation of expression of these neuropeptides in sensory neurons. METHODS: Pancreatitis was induced by retrograde infusion of trinitobenzene sulfonic acid into the pancreatic duct of adult rats. Three weeks post infusion continuous intrathecal infusion of the calcitonin gene-related peptide antagonist alpha CGRP8-37 or neurokinin-1 receptor antagonist CP-96345 or its inactive enantiomer CP-96344 was administered for seven days. The effects of treatment on pancreatic hyperalgesia were assessed by sensitivity of the abdominal wall to von Frey filament probing as well as by the nocifensive response to electrical stimulation of the pancreas. In a separate experiment chronic pancreatitis was induced and pancreas specific dorsal root ganglion neurons labeled with DiI were assessed for calcitonin gene-related peptide and substance P immunoreactivity. RESULTS: Intrathecal infusion of calcitonin gene-related peptide and neurokinin-1 receptor antagonists significantly attenuated behavioral pain responses in rats with chronic pancreatitis. Further, treatment of chronic pancreatitis rats with nerve growth factor antibody significantly reduced pancreas specific neurons expressing calcitonin gene-related peptide and substance P in thoracic dorsal root ganglion. CONCLUSIONS: Calcitonin gene-related peptide and substance P mediate pancreatic hyperalgesia in chronic pancreatitis and nerve growth factor in turn sustains the up-regulation of these neuropeptides in pancreatic sensory neurons. (+info)
What makes osteoarthritis painful? The evidence for local and central pain processing.
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In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans.
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Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 2: special populations.
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OBJECTIVE: To provide family physicians with a practical clinical summary of opioid prescribing for specific populations based on recommendations from the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. QUALITY OF EVIDENCE: Researchers for the guideline conducted a systematic review of the literature, focusing on reviews of the effectiveness and safety of opioids in specific populations. MAIN MESSAGE: Family physicians can minimize the risks of overdose, sedation, misuse, and addiction through the use of strategies tailored to the age and health status of patients. For patients at high risk of addiction, opioids should be reserved for well-defined nociceptive or neuropathic pain conditions that have not responded to first-line treatments. Opioids should be titrated slowly, with frequent dispensing and close monitoring for signs of misuse. Suspected opioid addiction is managed with structured opioid therapy, methadone or buprenorphine treatment, or abstinence-based treatment. Patients with mood and anxiety disorders tend to have a blunted analgesic response to opioids, are at higher risk of misuse, and are often taking sedating drugs that interact adversely with opioids. Precautions similar to those for other high-risk patients should be employed. The opioid should be tapered if the patient's pain remains severe despite an adequate trial of opioid therapy. In the elderly, sedation, falls, and overdose can be minimized through lower initial doses, slower titration, benzodiazepine tapering, and careful patient education. For pregnant women taking daily opioid therapy, the opioids should be slowly tapered and discontinued. If this is not possible, they should be tapered to the lowest effective dose. Opioid-dependent pregnant women should receive methadone treatment. Adolescents are at high risk of opioid overdose, misuse, and addiction. Patients with adolescents living at home should store their opioid medication safely. Adolescents rarely require long-term opioid therapy. CONCLUSION: Family physicians must take into consideration the patient's age, psychiatric status, level of risk of addiction, and other factors when prescribing opioids for chronic pain. (+info)
Central corticotropin-releasing factor (CRF) may attenuate somatic pain sensitivity through involvement of glucocorticoids.
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Corticotropin-releasing factor (CRF) is an important regulator of physiological functions and behavior in stress. Analgesia is one of the characteristics of stress reaction and CRF is involved in providing stress-induced analgesia, however, the underlying mechanisms remain to be determined. Exogenous CRF mimics stress effects on pain sensitivity and causes analgesic effect. The present study was performed to investigate the participation of endogenous glucocorticoids in analgesic effects induced by central administration of CRF in anesthetized rats. The participation of glucocorticoids was studied by pharmacological suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis as well as an occupation of glucocorticoid receptors by its antagonist RU 38486. Since CRF administration causes the release of beta-endorphin from the pituitary, the opioid antagonist naltrexone was used to determine the contribution of opioid-dependent mechanism to CRF-induced analgesia. An electrical current threshold test was applied for measurement of somatic pain sensitivity in anesthetized rats. Intracerebroventricular administration of CRF (2 mug/rat) caused analgesic effects (an increase of pain thresholds) and an increase in plasma corticosterone levels. Pretreatment with naltrexone did not change analgesic effects of central CRF as well as corticosterone levels in blood plasma. However, pharmacological suppression of the HPA axis leading to an inability of corticosterone release in response to CRF resulted in an elimination of CRF-induced analgesic effects. Pretreatment with RU 38486 also resulted in an elimination of CRF-induced effects. The data suggest that CRF-induced analgesic effects may be mediated by nonopioid mechanism associated with endogenous glucocorticoids released in response to central CRF administration. (+info)