The journal of pain : official journal of the American Pain Society
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From a treatment perspective, it is highly relevant to pinpoint individual vulnerability factors for resistance to exposure treatment in highly fearful chronic pain patients. Previous fear conditioning research showed that healthy individuals scoring relatively high on trait anxiety display sustained fear to safety cues during extinction. In the context of fear of movement-related pain, this intriguing question has been largely neglected so far. Even more importantly, positive psychological traits such as trait positive affect may function as protective factors against the spreading of fear to safe movements and improve exposure treatment outcomes. In this study, healthy participants completed a trait anxiety and trait positive affect questionnaire and underwent acquisition and extinction of fear of movement-related pain using an experimental voluntary movement paradigm. During acquisition, one movement (CS+) was paired with a painful stimulus and another movement was not (CS-). During extinction, the CS+ was no longer reinforced. Results show failure of fear inhibition to the CS- during extinction in healthy individuals scoring relatively high on trait anxiety or relatively low on positive affect. These findings seem to suggest that safety learning is more vulnerable in healthy people with a high anxious disposition and/or relatively lower levels of positive affect. In addition, this is the first study to show that the negative impact of high trait anxiety on fear inhibition to safety cues during extinction can be countered by high levels of positive affect. These findings may have important clinical implications. ⋯ Both low positive affect and high trait anxiety are associated with impaired fear inhibition to nonpainful movements during fear extinction. Interestingly, high levels of positive affect buffer against the negative impact of trait anxiety. Increasing positive affect during exposure may counter the effects of trait vulnerabilities and improve treatment outcomes.
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The effects of minocycline or riluzole treatment on spinal root avulsion-induced pain in adult rats.
Spinal root avulsion produces tactile and thermal hypersensitivity, neurodegeneration, and microglial and astrocyte activation in both the deafferented and the adjacent intact spinal cord segments. Following avulsion of the fifth lumbar spinal root, immediate and prolonged treatment with riluzole or minocycline for 2 weeks altered the development of behavioral hypersensitivity. Riluzole delayed the onset of thermal and tactile hypersensitivity and partially reversed established pain behavior. Minocycline effectively prevented and reversed both types of behavioral change. Histologic analysis revealed that both drugs reduced microglial staining in the spinal cord, with minocycline being more effective than riluzole. Astrocyte activation was ameliorated to a lesser extent. Surprisingly, neither drug provided a neuroprotective effect on avulsed motoneurons. ⋯ Immediate treatment of spinal root avulsion injuries with minocycline or riluzole prevents the onset of evoked pain hypersensitivity by reducing microglial cell activation. When treatment is delayed, minocycline, but not riluzole, reverses pre-established hypersensitivity. Thus, these drugs may provide a new translational treatment option for chronic avulsion injury pain.
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Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids. ⋯ This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine.
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Review Meta Analysis
Associations between pain appraisals and pain outcomes: meta-analyses of laboratory pain and chronic pain literatures.
In this research, meta-analyses were performed to evaluate associations between primary appraisals of pain as a source of threat and/or challenge and responses to 1) noxious laboratory stimuli and 2) chronic noncancer pain. Twenty-two laboratory pain studies comprising 2,031 participants and 59 chronic pain studies based on 9,135 patients were identified for analysis. For laboratory pain, elevated threat appraisals were linked to overall increases in reported pain, reduced pain tolerance, and high levels of passive coping. Method of measuring appraisal as well as type and duration of noxious stimulation moderated some of these associations. Challenge appraisals were related to more pain tolerance and less passive coping but not pain intensity. For chronic pain studies, threat appraisals had positive overall correlations with pain intensity, impairment, affective distress, and passive coping but were negatively related to active coping. The pattern of associations between challenge appraisals and outcomes was largely complementary. Appraisal scale used and gender were consistent moderators of appraisal-outcome relations in chronic pain samples. In sum, appraisals of pain as a source of potential damage or opportunity have robust associations with responses to acute laboratory pain and ongoing chronic pain. ⋯ Meta-analyses evaluated associations between primary appraisals and responses to laboratory pain and chronic pain. Significant effect sizes for most outcomes suggest that appraisals of pain as a source of threat and challenge have important implications for functioning in response to pain.
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Randomized Controlled Trial
Intranasal fentanyl versus fentanyl pectin nasal spray for the management of breakthrough cancer pain in doses proportional to basal opioid regimen.
The aim of this randomized, crossover, comparison study was to assess the analgesic and adverse effects of 2 nasal preparations, intranasal fentanyl (INFS) and fentanyl pectin nasal spray (FPNS), for breakthrough pain, given in doses proportional to opioid basal regimen. Each patient randomly received INFS or FPNS in doses proportional to opioid dosages used for background analgesia for 2 pairs of episodes. For each episode of breakthrough pain, pain intensity and adverse effects intensity were recorded just before starting the INFS or FPNS (T0) and 5 minutes (T5), 10 minutes (T10), and 20 minutes (T20) after the administration of the nasal drugs. Sixty-nine patients were studied. The mean age was 63.4 years, and 37 patients were males. For the present analysis, 188 episodes were considered. A statistical decrease in pain intensity was observed with both nasal drugs after 5, 10, and 20 minutes. A decrease in pain intensity of >33% was observed in 16, 102, and 159 treated episodes at T5, T10, and T20, respectively. Adverse effects were of mild nature in most cases or were preexistent because of basal opioid therapy. No differences were found in summed pain intensity difference 20 minutes after dosing. Most of patients did not find substantial preferences. INFS and FPNS were effective and well-tolerated treatments for breakthrough pain management. Both delivery systems, in doses proportional to the basal opioid regimen, provided significant analgesia within 10 minutes, without producing relevant adverse effects. ⋯ This article showed that INFS and FPNS in doses proportional to basal opioid regimen are equally safe and effective for the management of breakthrough pain in cancer patients. These data provide new insights on the use of nasal preparations of fentanyl.