None listed
Conditions
Brief summary
A major early component of neuropathic pain is infiltration of immune cells into the injured tissue that release inflammatory mediators. These mediators could either directly, or through the induction of neurotrophic factors, trigger increased alpha-1 adrenoceptor expression on neurons and other cells around the site of injury. In turn, activation of alpha-1 adrenoceptors on fibroblasts and keratinocytes may trigger further release of growth factors and inflammatory mediators. Thus, an upward spiral of alpha-1 adrenoceptor expression on these cells and on regenerating neurons could engender an adrenergic component of inflammation and pain. The aim of this project is to investigate this hypothesis in a large sample of patients with complex regional pain syndrome and in other forms of painful neuropathy. An adrenergic component of pain in the skin will be assessed in response to intradermal injection of the adrenergic agonists phenylephrine and clonidine. In addition, we will investigate the expression of alpha-1 adrenoceptors and inflammatory mediators in skin biopsies of hyperalgesic and control skin. This project may have significant treatment implications, as blocking up-regulation of the alpha-1 adrenoceptor could ultimately prove to be a useful therapeutic strategy for patients with an adrenergic component of pain.
Interventions
We will identify patients with an adrenergic component of pain by assessing their response to phenylephrine injected intradermally (0.05 mg injected once only into the affected limb, and 0.05 mg injected simultaneously into the opposite unaffected limb). Phenylephrine will be administered by a pain specialist or by qualified personnel under medical supervision. Phenylephrine may induce pain at the site of injection for 10-40 minutes in symptomatic skin of patients with an adrenergic component of
We will identify patients with an adrenergic component of pain by assessing their response to phenylephrine injected intradermally (0.05 mg injected once only into the affected limb, and 0.05 mg injected simultaneously into the opposite unaffected limb). Phenylephrine will be administered by a pain specialist or by qualified personnel under medical supervision. Phenylephrine may induce pain at the site of injection for 10-40 minutes in symptomatic skin of patients with an adrenergic component of pain but is not expected to induce pain in nonsymptomatic skin. Sensitivity to pinprick stimulation will be investigated at and around the site of injection before and every 10 minutes after the injection for 40 minutes. At the end of the study, a skin biopsy will be obtained from the affected limb and contralateral limb for comparison, and the distribution of a biomarker (the alpha-1 adrenoceptor) will be examined using immunohistochemistry.
Sponsors
Murdoch University
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Diagnosis
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
meets "Budapest" criteria for complex regional pain syndrome; or meets clinical criteria for other forms of neuropathic pain.
Exclusion criteria
Participants will be excluded if they are pregnant or breastfeeding, if they have a medical condition that affects their heart, blood vessels, skin, liver or kidneys that requires regular treatment with medication, if they have a known sensitivity to adrenergic drugs, or have severe hypertension, arrhythmias, hyperthyroidism or hyperglycaemia.
Outcome results
None listed