112 research outputs found
The role of galanin and neuropeptide Y in a rat model of neuropathic pain
Galanin and neuropeptide Y (NPY) are not normally produced to any significant
extent by primary afferent neurones. After peripheral nerve injury however, there is a
marked increase in their synthesis - galanin mainly in small to medium sized
neurones, and NPY mainly in large neurones. There is evidence of transport ofthese
newly produced peptides to the dorsal horn, but it is not known what stimuli result in
their release in the spinal cord. The antibody microprobe technique was therefore
used to study the factors that might result in release of these peptides. The model
that has been studied involved placement of four loose ligatures around one sciatic
nerve in the rat, reliably resulting in the development of behavioural evidence of
neuropathic pain.In addition to observing for the characteristic signs associated with this model, the
development of neuropathic pain was assessed quantitatively by the paw withdrawal
response to von Frey hairs and pin prick. Thus, all the animals used in the study of
peptide release or functional changes in the spinal cord, 10 to 14 days later, did
indeed have evidence of neuropathic pain.A general assessment of altered spinal cord responses, found significant changes in
the neuropathic rats. There was found to be a bilateral increase in the cord dorsum
potentials evoked by A fibre stimulation of the injured nerve, as compared tot he
normal nerve, despite a decrease in the afferent volley from the injured nerve. As the
synthesis of both galanin and NPY is stimulated by peripheral nerve injury,
alterations in their spinal release was studied, including the effects of A fibre
stimulation on this central release.Microprobes bearing immobilised antibodies to galanin were inserted into the spinal
cord of neuropathic rats. An increased area of immunoreactive (ir)-galanin release
was detected in the superficial dorsal horn ipsilateral to nerve injury, as compared to
that normally found. This occurred in the absence of any active peripheral
stimulation, in an area of the dorsal horn where the small primary afferent fibres that
have started to synthesise galanin terminate. Ir-galanin release was not increased by
electrical stimulation of the injured nerve at a strength sufficient to activate A fibres, but there was an increase in release as C fibres were stimulated. Conduction block
proximal to the dorsal root ganglia did not reduce the increased basal ir-galanin
release found ipsilateral to the nerve injury. An increase in ir-galanin release was
seen, however, on the contralateral side of the cord, after all neuronal input had been
blocked from the injured nerve.Previous studies in this laboratory have found that, on the side ipsilateral to nerve
injury, ir-NPY was released spontaneously in the dorsal horn and this release was
increased by electrical stimulation of the injured nerve sufficient to activate only A
fibres. The large diameter primary afferent neurones that synthesise NPY after nerve
injury terminate in the deep dorsal horn, where ir-NPY was released, making it
probable that these fibres are the source of this ir-NPY. Using antibody coated
microprobes, the present studies found that the spontaneous release of ir-NPY was
not altered by conduction block ofthe injured nerve proximal to the dorsal root
ganglia. It appears therefore, that release ofNPY in the spinal cord from large
diameter primary afferent neurones does not require any peripheral neuronal
impulses.The large diameter neurones that start to produce NPY express the neurotrophin-3
(NT-3) receptor, trkC. It has also been shown that exogenous NT-3 can attenuate
some of the increases in spinal levels ofNPY, after bilateral axotomy. The effect of
exogenous NT-3 on NPY release was therefore studied using a chronic infusion of
NT-3 delivered to the nerve injury site and antibody microprobes to measure
spontaneous NPY release. It was found that NT-3 infusion had no effect on
spontaneous NPY release, but a minor alleviation of mechanical hypersensitivity was
noted 10 to 14 days after nerve injury, in those rats receiving exogenous NT-3.
These studies have determined some of the stimuli responsible for spinal release of
galanin and NPY after peripheral nerve injury, and excluded others. Further work is
required to correlate these results with functional effects and possible role in the
modulation of nociceptive transmission
Peri-operative opioid analgesia - when is enough too much? A review of opioid-induced tolerance and hyperalgesia
The impact of relocation of chronic pain service from hospital setting to community centre on patient experience:a single-centre audit
Examination of the clinical factors associated with attendance at emergency departments for chronic pain management and the cost of treatment relative to that of other significant medical conditions
The effect of adverse childhood experiences on chronic pain and major depression in adulthood:a systematic review and meta-analysis
Effect of a continuous perineural levobupivacaine infusion on pain after major lower limb amputation:a randomised double-blind placebo-controlled trial
Acknowledgments: We would like to acknowledge the assistance of Dr M Viskaduraki, University of Leicester, UK for additional statistical advice; and both Prof D.J. Rowbotham and Mr M. McCarthy, University Hospitals of Leicester NHS Trust, for advice on the trial protocol.Peer reviewedPublisher PD
Pain Management in Cancer Center Inpatients:A Cluster Randomized Trial to Evaluate a Systematic Integrated Approach—The Edinburgh Pain Assessment and Management Tool
Purpose
Pain is suboptimally managed in patients with cancer. We aimed to compare the effect of a policy of adding a clinician-delivered bedside pain assessment and management tool (Edinburgh Pain Assessment and management Tool [EPAT]) to usual care (UC) versus UC alone on pain outcomes.
Patients and Methods
In a two-arm, parallel group, cluster randomized (1:1) trial, we observed pain outcomes in 19 cancer centers in the United Kingdom and then randomly assigned the centers to either implement EPAT or to continue UC. The primary outcome was change in the percentage of study participants in each center with a clinically significant (≥ 2 point) improvement in worst pain (using the Brief Pain Inventory Short Form) from admission to 3 to 5 days after admission. Secondary outcomes included quality of analgesic prescribing and opioid-related adverse effects.
Results
Ten centers were randomly assigned to EPAT, and nine were assigned to UC. We enrolled 1,921 patients and obtained outcome data from 93% (n = 1,795). Participants (mean age, 60 years; 49% women) had a variety of cancer types. For centers randomly assigned to EPAT, the percentage of participants with a clinically significant improvement in worst pain increased from 47.7% to 54.1%, and for those randomly assigned to continue UC, this percentage decreased from 50.6% to 46.4%. The absolute difference was 10.7% (95% CI, 0.2% to 21.1%; P = .046) and it increased to 15.4% (95% CI, 5.8% to 25.0%; P = .004) when two centers that failed to implement EPAT were excluded. EPAT centers had greater improvements in prescribing practice and in the Brief Pain Inventory Short Form pain subscale score. Other pain and distress outcomes and opioid adverse effects did not differ between EPAT and UC.
Conclusion
A systematic integrated approach improves pain outcomes for inpatients in cancer centers without increasing opioid adverse effects
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