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Table 4 Studies on the role of CGRP in neuropathic pain

From: Calcitonin gene-related peptide and pain: a systematic review

Study Objectives Reported pain as part of phenotype Method and sample size Source of CGRP Results Duration of the investigated condition Correlation between CGRP level and pain
Albrecht, 2006 [1] Investigate CGRP expression in skin from amputated extremity affected by CRPS CRPS after amputation in upper and lower limbs Skin tissue from 2 patients and 5 controls Tissue biopsies
(skin)
Loss of CGRP expression in CRPS patients NR NR
Attal, 2016 [2] Determine CGRP levels in peripheral neuropathic pain patients after treatment with botulinum toxin A Peripheral neuropathic pain, mixed group ELISA of biopsy from 23 patients with active treatment and 17 patients with placebo treatment at week 1 and 4 after study start Skin No change in CGRP levels at week 4 compared to week 1. Average pain score was not changed either NR None
Awawdeh, 2002 [3] Investigate presence of CGRP in the gingival crevicular fluid of teeth diagnosed with pain of pulpal origin Tooth pain Gingival crevicular fluid from a painful and non-painful site from 54 patients undergoing pulpectomy. 1 week after fluid was collected from 21 patients Gingival crevicular fluid No difference in CGRP-levels between painful tooth compared to the contralateral control tooth NR No clear association between CGRP-levels and dental pain
Boras, 2010 [4] Determine saliva and serum CGRP levels in patients with BMS Burning mouth syndrome Saliva and serum from 26 patients and 22 controls Saliva and serum No difference between patients and controls NR NR
Birklein, 2001 [5] Test contribution of neuropeptide release to pathophysiology of CRPS CRPS in upper or lower limbs Serum CGRP concentrations were measured in 19 patients on the affected (n = 19) side and non-affected side (n = 13) before and 9 months after therapy (n = 9). Comparison with controls (n = 16) Blood
(serum)
Increased CGRP levels in CRPS patients.
No difference in CGRP levels in blood taken from affected versus non-affected side.
After therapy – normalization of CGRP levels compared to healthy controls
Mean 29 weeks (range: 2 to 188 weeks) No correlation between CGRP-levels and pain
Chavarría-Bolanos, 2014 [6] Determine CGRP-levels in dental pulp tissue samples from 8 patients subjected to undergo controlled orthodontic intrusive forces Tooth pain Human premolar dental pulp tissue was extracted from 8 patients, and 8 controls Tissue biopsies
(dental pulp)
No differences in CGRP levels between the two groups 24 h NR
Hou, 2011 [7] Determine whether CGRP-IL is increased among epidermal keratinocytes in PHN and diabetes PHN and small fiber neuropathy Punch biopsies from 5 patients with PHN from painful areas, 5 patients with diabetes (biopsies from feet) and 11 controls Tissue biopsies
(skin)
Increased CGRP-levels in keratinocytes from PHN patients compared to controls NR CGRP levels were higher in painful skin areas compared to non-painful locations
Kalliomäki, 2011 [8] Investigate structural and functional differences between patients with and without chronic pain following nerve injury Hand pain due to nerve injury Skin biopsies from 21 patients with pain and 9 controls without pain. All participants required hand surgery Tissue biopsies
(skin)
No difference in CGRP-staining between patients and controls >1 year No significant difference between pain and non-pain patients
Lindqvist. 2000 [9] Examine CGRP expression in painful Morton’s neuroma patients Forefoot Morton’s neuroma 11 nerve biopsies from 8 patients and 4 controls Nerve biopsies Increased levels of CGRP-IR nerve fibers compared to controls NR NR
Schinkel, 2009 [10] Compare systemic inflammatory mediators in patients with CRPS I with controls CRPS in the upper limb Blood samples were obtained from 22 patients. 12 patients had chronic CRPS and 10 patients had acute CRPS. Patients were compared to 8 controls Blood
(plasma)
CGRP-levels were lower in chronic CRPS patients, compared to controls Acute: < 6 months
Chronic: > 6 months
NR
Zidverc-Trajkovic, 2009 [11] Determine saliva CGRP levels in patients with BMS Burning mouth syndrome Saliva from 78 patients and 16 healthy controls Saliva Inconclusive, CGRP levels were non-significantly decreased in comparison to controls At least 6 months NR
  1. BMS Burning mouth syndrome, CRPS Complex regional pain syndrome, CSF Cerebrospinal fluid