Table 1 Studies on the role of CGRP in somatic 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 |
|---|---|---|---|---|---|---|---|
Alpar, 2002 [1] | Determine plasma CGRP in patients with whiplash injury who were treated by carpal tunnel decompression | Chronic shoulder and neck pain due to whiplash injury | 38 patients and 11 controls. Enzyme-immunoassay kit was used to measure the plasma CGRP | Blood (plasma) | Mean plasma levels was higher in patients, 400Â ng/l, than in controls, 85Â ng/l. Plasma levels were reduced, 65Â ng/l, after carpal tunnel decompression | NR | Reduced plasma CGRP after the operation correlated to the pain reduction |
Bjur, 2005 [2] | Investigate innervation patterns of Achilles tendon in tendinosis tendon, and normal tendon | Chronic pain in tendinosis | Tissue samples from 21 patients and 9 controls | Tissue biopsies (Achilles tendon) | Inconclusive. CGRP was found in both patients and controls. The amount of CGRP-fibers was not quantified | Mean 19Â months | NR |
Brown, 1997 [3] | Determine density of CGRP containing sensory nerve fibers in vertebral endplate in patients with degenerative disc disease | Severe back pain with or without sciatica in degenerative disc disease | Tissue from the intervertebral discs from 15 patients undergoing anterior lumbar discectomy and 7 healthy post-mortem controls | Tissue biopsies (intervertebral discs) | Marked increase in CGRP-containing sensory nerve fibers compared with controls | NR | NR |
Carlsson, 2006 [4] | Evaluate possible effects of acupuncture on sensory nerve fibers in human skin | Cervicobrachial pain, cervicocranial pain, hip pain and finger pain from arthrosis | Punch skin biopsies taken from 6 patients one week before acupuncture and 3–6 days after the 10th treatment | Tissue biopsies (skin) | The mean number of CGRP-IR nerve fibers were reduced after treatment | 4 months - >10 years | NR |
Danielson, 2008 [5] | Investigate CGRP prevalence in patients with tendinitis surgery. | Chronic painful patellar tendinosis | Patellar tendon biopsy in 7 patients | Tissue biopsies (patellar tendon) | CGRP rarely detected at perivascular sites | Chronic pain | NR |
Dong, 2015 [6] | Examine CGRP concentrations in patients with primary knee OA and controls | Chronic knee pain from OA | Serum CGRP concentrations in OA patients (n = 65) and controls (n = 21). | Blood (serum) | CGRP levels were higher in patients, 2.43 ng/mL, than in controls, 1.95 ng/mL | NR | CGRP concentrations in serum were correlated with pain intensity |
Ikeuchi, 2012 [7] | Determine sensory innervation of posterior cruciate ligament (PCL) in patients with OA | Chronic knee pain from OA | PCL samples from 10 patients and 5 pain-free controls with anterior cruciate ligament (ACL) rupture | Tissue biopsies (joint ligament) | No difference between patients and controls | NR | NR |
Jonhagen, 2006 [8] | Determine CGRP in human skeletal muscle at rest and after painful eccentric exercise | Experimental muscle pain after eccentric exercise | Microdialysis catheter inserted in quadriceps muscle in 8 healthy volunteers. Samples taken before and after exercise. | Blood (plasma) | CGRP levels were higher 2 days after exercise, 5.4 fmol/ml, than directly after exercise, 4.85 fmol/ml | VAS-score was assessed on the entry day (VAS = 0), day 1 (VAS = 1) and day 3 (VAS = 2) after the exercise | CGRP concentrations was positively correlated with pain intensity (VAS) |
Larsson, 1991 [9] | Investigate CGRP-levels from patients with rheumatoid arthritis and patients with meniscal/cruciate ligament injuries | Acute knee pain in meniscal/cruciate ligament injuries | Synovial fluid from the knee joint of 18 patients and 13 pain-free controls with ligament injuries | Synovial fluid (knee joint) | Increased CGRP levels in patients compared to controls. | 4-27 years | NR |
Lin, 2015 [10] | Investigate associations between plasma CGRP-levels and clinical outcome from APA, in patients with osteoarthritis and spinal stenosis | Chronic lower back pain (CLBP) in patients with osteoarthritis and spinal stenosis | Blood samples from 32 patients (APA-group) and 29 controls (sham APA-group). Samples were taken at baseline and 4Â weeks later. VAS-score before treatment was 4. | Blood (plasma) | Patients showed a decrease in CGRP levels after treatment. No decrease in the control group | At least 3Â months | 56% of the patient group reported a reduction in pain, whereas only 9% controls reported a reduction |
Lindh, 1999 [11] | Determine CGRP-LI levels in CSF in patients with chronic pain | Osteoarthritis, herniated lumbar disc and hip fracture pain | Sample: CSF Subjects: 35 patients (14 had knee or hip pain, 11 had rhizopathic pain due to herniated lumbar pain, 10 had pain from hip fracture and 12 healthy controls. Pain assessment: VAS | CSF | Decreased CGRP-LI levels were observed in patients compared to healthy controls | Osteoarthritis patients: >6 months. Rhizopathic pain: At least 1 month (1–13). Hip fracture pain: Up to 48 h | No correlation between CGRP-LI levels and VAS-values could be observed for any of the subjects participating in the study |
Onuoha, 1999 [12] | Investigate CGRP levels in patients with soft tissue injury | Acute muscle and ligament pain due to injury | Plasma CGRP-concentrations in 17 patients and 15 healthy controls | Blood (Plasma) | CGRP-levels were significantly higher in patients than controls | Up to 24Â h | NR |
Ozawa, 2006 [13] | To determine sensory fibers innervating human degenerated lumbar intervertebral discs | Discogenic low back pain | Lumbar intervertebral disc was harvested from 8 patients, and immunostained for CGRP | Tissue biopsies (intervertebral disc) | CGRP-IR nerve fibers were observed in 6 out of 8 patients | NR | NR |
Samuelsson, 1993 [14] | Determine CSF CGRP levels in cancer patients | Cancer pain | CSF from 10 patients compared with 10 controls | CSF | No difference in CGRP-levels between patients and controls | NR | No difference between patients with pain and controls |
Sasaki, 2013 [15] | Investigate innervation patterns of ECRB in patients with recalcitrant tennis elbow | Lateral epicondylitis | Tissue biopsies from 8 patients and 2 controls. The control group suffered from osteochondritis | Tissue biopsies (lateral epicondyle) | A decrease in the immunorectivity of CGRP compared to controls | Mean duration 23Â months | The innervation pattern did not appear to be correlated with VAS-score |
Sato, 2004 [16] | Elucidate expression of CGRP in temporomandibular joint (TMJ) from patients with internal derangement | TMJ pain | Synovial fluid from 48 patients and 7 controls, who had pain-free habitual dislocation | Synovial fluid (TMJ) | Increased CGRP in patients compared to controls | Mean duration 6Â months | Positive correlation between the extent score of CGRP-levels and joint pain |
Saxler, 2007 [17] | Determine presence of CGRP-immunopositive nerve fibers in patients with OA | Hip pain from OA | Soft tissue biopsies from fossa acetabuli in 3 patients and 6 pain-free controls. 3 controls had a failed THA and 3 controls had femoral neck fractures | Tissue biopsies (fossa acetabuli) | Increased CGRP-LI in patients compared to controls. | NR | Positive correlation between CGRP and pain |
Takeshita, 2012 [18] | Clarify sensory innervation and inflammatory cytokines in OA patients | Severe hip pain from OA | Synovium from 50 patients and 12 controls with femoral neck fracture | Synovial fluid (hip) | CGRP-IR sensory nerve fibers were observed in 54% of the patients and 0% in controls | NR | NR |
Takeuchi, 2007 [19] | Determine CGRP’s role in patients with lumbar disc herniation, before and after lumbar discectomy | Sciatic pain/lumbar disc herniation | Plasma CGRP was measured in 27 patient before and 3 weeks after lumbar discectomy | Blood (plasma) | Plasma CGRP-levels were reduced after lumbar discectomy | 3 weeks | Reduced plasma CGRP after the operation correlated to lower VAS-levels |
Wang, 2015 [20] | Explore mechanisms of possible involvement and regulation of CGRP in pathological and inflammatory processes of arthritis in patients with developmental dysplasia of the hip (DDH) | Hip pain from OA | Synovial tissue samples from 67 patients: 35 with moderate DDH and 32 patients with severe DDH. 15 controls with traumatic femoral fracture | Synovial tissue (fossa acetabuli) | Increased CGRP in synovium fluid from patients in the severe DDH group compared to the moderate DDH group and controls | NR | The highest amount of CGRP correlated with the highest VAS |