Non-Cochrane · prognostic · PM42056954
Neural biomarkers in pulpitis and their associations with inflammation and pain perception: a systematic review and meta-analysis.
Cen Rong, Dai Yuguo, Li Kar Yan, et al. · BMC oral health · 2026 · PubMed · doi:10.1186/s12903-026-08438-9
Findings
Population Permanent teeth with symptomatic irreversible pulpitis (SIP)
2 findings
| Symptomatic irreversible pulpitis (inflamed pulp) | Healthy pulp (normal pulp, NP) | Calcitonin gene-related peptide (CGRP) expression level in dental pulp | SMD 2.973 [0.553, 5.393] Low Downgraded: imprecision 5 studies · 188 participants |
| Symptomatic irreversible pulpitis (inflamed pulp) | Healthy pulp (normal pulp, NP) | Substance P (SP) expression level in dental pulp | SMD 3.108 [0.008, 6.208] Very low Downgraded: imprecision 4 studies · 127 participants |
Included primary studies 64
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| De Arruda 2023 Relaxation of smooth muscle following contraction elicited by sympathetic nerve stimulation in vivo. PMID:202357 | 1977 | 3 other reviews | not stated | not extracted yet |
| Awawdeh 2002 Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. PMID:11853236 | 2002 | 1 other review | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Bowles 2003 Tissue levels of immunoreactive substance P are increased in patients with irreversible pulpitis. PMID:12701777 | 2003 | 1 other review | Substance P (SP) expression level in dental pulp | not extracted yet |
| Castillo-Silva 2019 Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema. PMID:201954 | 1977 | 1 other review | Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Castillo-Silva 2019 Expression of calcitonin gene-related peptide and pulp sensitivity tests in irreversible pulpitis. PMID:31531564 | 2019 | 1 other review | Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2004 Expression of calcitonin gene-related peptide (CGRP) in irreversible acute pulpitis. PMID:15085045 | 2004 | 1 other review | Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2005 Calcitonin gene-related peptide receptor expression in healthy and inflamed human pulp tissue. PMID:16164685 | 2005 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2006 Quantification of neuropeptides (calcitonin gene-related peptide, substance P, neurokinin A, neuropeptide Y and vasoactive intestinal… PMID:16640639 | 2006 | 1 other review | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2007 Macular influences on somatosensory transmission through the spinoreticulocerebellar pathway. PMID:200740 | 1977 | 1 other review | not stated | not extracted yet |
| Caviedes-Bucheli 2008 Calcitonin gene-related peptide receptor expression in alternatively activated monocytes/macrophages during irreversible pulpitis. PMID:18634925 | 2008 | 1 other review | not stated | not extracted yet |
| Mehboob 2021 False negative bone scans in neuroblastoma metastatic to the ends of long bones. PMID:202156 | 1978 | 1 other review | not stated | not extracted yet |
| Morgan 2009 The pathogenesis of endocrine exophthalmos: a short review. PMID:200947 | 1977 | 1 other review | not stated | not extracted yet |
| Sattari 2010 Substance P and CGRP expression in dental pulps with irreversible pulpitis. PMID:20666750 | 2010 | 1 other review | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Suwanchai 2012 A glycine to serine substitution identifies the CYP 3 locus as the structural gene of iso 2 cytochrome c in Saccharomyces cerevisiae. PMID:201250 | 1977 | 1 other review | not stated | not extracted yet |
| Yang 2024 The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine… PMID:202459 | 1977 | 1 other review | not stated | not extracted yet |
| Alvarado 2007 TRPM8 Axonal expression is decreased in painful human teeth with irreversible pulpitis and cold hyperalgesia. PMID:17889683 | 2007 | this review only | not stated | not extracted yet |
| Alvarado 2007 Synaptic excitation and inhibition resulting from direct action of acetylcholine on two types of chemoreceptors on individual amphibian… PMID:200739 | 1977 | this review only | not stated | not extracted yet |
| Awawdeh 2002 Enzyme-bound early product of purified poly(ADP-ribose) polymerase. PMID:200230 | 1977 | this review only | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Bakri 2018 Excretion of feline leukaemia virus by naturally infected pet cats. PMID:201852 | 1977 | this review only | not stated | not extracted yet |
| Bakri 2018 Transient receptor potential vanilloid 4 (TRPV4) expression on the nerve fibers of human dental pulp is upregulated under inflammatory… PMID:29499561 | 2018 | this review only | not stated | not extracted yet |
| Beneng 2010 Methanethiol inhibition of mitochondrial respiration. PMID:201048 | 1977 | this review only | not stated | not extracted yet |
| Beneng 2010 Sodium channel Na v 1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome. PMID:20529324 | 2010 | this review only | not stated | not extracted yet |
| Bowles 2003 An attenuated mink enteritis virus and its use in a trivalent vaccine: studies on safety and antigenicity. PMID:200331 | 1977 | this review only | Substance P (SP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2004 Effect of exercise and of prolonged oral administration of propranolol on haemodynamic variables, plasma renin concentration, plasma… PMID:200433 | 1977 | this review only | Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2005 [Modification of the kinetics of adipose tissue lipoprotein lipase by heparin (author's transl)]. PMID:200534 | 1977 | this review only | not stated | not extracted yet |
| Caviedes-Bucheli 2006 The development and degeneration of Purkinje cells in pcd mutant mice. PMID:200636 | 1978 | this review only | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Caviedes-Bucheli 2007 Substance P receptor expression in healthy and inflamed human pulp tissue. PMID:17229115 | 2007 | this review only | not stated | not extracted yet |
| Caviedes-Bucheli 2008 Synchronised transmembrane insertion and glycosylation of a nascent membrane protein. PMID:200844 | 1977 | this review only | not stated | not extracted yet |
| da Silva 2008 Action of nitric oxide on healthy and inflamed human dental pulp tissue. PMID:18337111 | 2008 | this review only | not stated | not extracted yet |
| da Silva 2008 Human virus-infected target cells lacking HLA antigens resist specific T-lymphocyte cytolysis. PMID:200845 | 1977 | this review only | not stated | not extracted yet |
| de Arruda 2023 Evaluation of the expression of nerve fiber markers in healthy and inflamed dental pulp. PMID:36790260 | 2023 | this review only | not stated | not extracted yet |
| Dincer 2020 Lethal intestinal virus of infant mice is mouse hepatitis virus. PMID:202055 | 1977 | this review only | not stated | not extracted yet |
| Dincer 2020 Comparison of Neurokinin A, Substance P, Interleukin 8, and Matrix Metalloproteinase-8 Changes in Pulp tissue and Gingival Crevicular… PMID:32702349 | 2020 | this review only | not stated | not extracted yet |
| Dong 2013 [Effect of NADH and several Krebs cycle substrates on the endogenous metabolism of Pseudomonas fluorescens (type S)]. PMID:201351 | 1977 | this review only | not stated | not extracted yet |
| Dong 2013 Increased expression of EphA7 in inflamed human dental pulp. PMID:23321235 | 2013 | this review only | not stated | not extracted yet |
| Dourou 2006 Comparative evaluation of neural tissue antigens--neurofilament protein (NF), peripherin (PRP), S100B protein (S100B), neuron-specific… PMID:16919707 | 2006 | this review only | not stated | not extracted yet |
| Dourou 2006 The effects of formocresol on rat sponge implant tissue: a biochemical study. PMID:200637 | 1977 | this review only | not stated | not extracted yet |
| Israr 2023 Kinin, kininogen and kininase levels during acute Babesia bovis (= B. argentina) infection of cattle. PMID:202358 | 1977 | this review only | not stated | not extracted yet |
| Israr 2023 Investigating In Situ Expression of Neurotrophic Factors and Partner Proteins in Irreversible Pulpitis. PMID:37660765 | 2023 | this review only | not stated | not extracted yet |
| Mehboob 2021 Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity. PMID:34041298 | 2021 | this review only | not stated | not extracted yet |
| Morgan 2005 Vanilloid receptor 1 expression in human tooth pulp in relation to caries and pain. PMID:16106719 | 2005 | this review only | not stated | not extracted yet |
| Morgan 2005 Insulin release from collagenase-isolated islets of rat pancreas in the presence of cyclic AMP and somatostatin. PMID:200535 | 1977 | this review only | not stated | not extracted yet |
| Morgan 2009 Changes in proteinase-activated receptor 2 expression in the human tooth pulp in relation to caries and pain. PMID:19639106 | 2009 | this review only | not stated | not extracted yet |
| Renton 2003 Capsaicin receptor VR1 and ATP purinoceptor P2X3 in painful and nonpainful human tooth pulp. PMID:14520770 | 2003 | this review only | not stated | not extracted yet |
| Renton 2003 Chemotherapy of malignant fibrous histiocytoma: a Southwest Oncology Group report. PMID:200332 | 1977 | this review only | not stated | not extracted yet |
| Rodd & Boissonade 2000 [Activity of the enzymes of glucose-6-phosphate metabolism in the tissues of hepatomas with different growth rates]. PMID:200028 | 1977 | this review only | not stated | not extracted yet |
| Rodd & Boissonade 2001 Clinical cyclic nucleotide research. PMID:200129 | 1977 | this review only | not stated | not extracted yet |
| Rodd 2000 Substance P expression in human tooth pulp in relation to caries and pain experience. PMID:11153921 | 2000 | this review only | not stated | not extracted yet |
| Rodd 2001 Innervation of human tooth pulp in relation to caries and dentition type. PMID:11269734 | 2001 | this review only | not stated | not extracted yet |
| Rowland 2007 TRPM2 immunoreactivity is increased in fibroblasts, but not nerves, of symptomatic human dental pulp. PMID:17320705 | 2007 | this review only | not stated | not extracted yet |
| Rowland 2007 [Norepinephrine interference in adrenal hormone balance related to blood calcium effects of PTH (author's transl)]. PMID:200741 | 1977 | this review only | not stated | not extracted yet |
| Sattari 2010 Induction of cleft palate in hamster fetus following prenatal treatment with ACTH. PMID:201049 | 1977 | this review only | Substance P (SP) expression level in dental pulp; Calcitonin gene-related peptide (CGRP) expression level in dental pulp | not extracted yet |
| Steiner 2018 Recent excitement in the DNA replication problem. PMID:201853 | 1977 | this review only | not stated | not extracted yet |
| Steiner 2018 Secretoneurin and PE-11 immunoreactivity in the human dental pulp. PMID:29132068 | 2018 | this review only | not stated | not extracted yet |
| Suwanchai 2012 NaV 1.8, but not NaV 1.9, is upregulated in the inflamed dental pulp tissue of human primary teeth. PMID:22085016 | 2012 | this review only | not stated | not extracted yet |
| Wadachi & Hargreaves 2006 A laboratory evaluation of the effect of two surface-wetting treatments on soft denture liners. PMID:200638 | 1977 | this review only | not stated | not extracted yet |
| Wadachi 2006 Trigeminal nociceptors express TLR-4 and CD14: a mechanism for pain due to infection. PMID:16373680 | 2006 | this review only | not stated | not extracted yet |
| Warren 2008 Quantification of neural protein in extirpated tooth pulp. PMID:18155483 | 2008 | this review only | not stated | not extracted yet |
| Warren 2008 Is alpha MSH a trophic hormone to adrenal function in the foetus? PMID:200846 | 1977 | this review only | not stated | not extracted yet |
| Wells 2007a Expression of Nav1.9 channels in human dental pulp and trigeminal ganglion. PMID:17889684 | 2007 | this review only | not stated | not extracted yet |
| Wells 2007a [Placental and fetal growth in the rabbit: influence and mechanism of action of ovarian hormones (author's transl)]. PMID:200742 | 1977 | this review only | not stated | not extracted yet |
| Wells 2007b Kv1.4 subunit expression is decreased in neurons of painful human pulp. PMID:17804321 | 2007 | this review only | not stated | not extracted yet |
| Wells 2007b Problem solving revisited. PMID:200743 | 1977 | this review only | not stated | not extracted yet |
| Yang 2024 Expression patterns of mechanosensitive ion channel PIEZOs in irreversible pulpitis. PMID:38627713 | 2024 | this review only | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Permanent teeth diagnosed with or exhibiting symptoms of pulpitis or pulp exposure | Permanent teeth with pulpitis (n=32 case-control studies) |
| Intervention | Molecular biomarkers of neural changes (nerve growth factors, ion channels, neurotransmitters, neuropeptides, receptors) measured in dental pulp or pulpal blood | 38 neural biomarkers investigated; SP (n=4 in meta-analysis), CGRP (n=5 in meta-analysis) |
| Comparison | Healthy pulp of permanent teeth | Normal pulp (NP) |
| Outcomes | Difference in biomarker expression between inflamed and healthy pulp; association with severity of pulpal inflammation and pain perception | Biomarker expression in symptomatic irreversible pulpitis vs normal pulp; correlation with pain (NK-1R, Nav1.8, PIEZO2, 1 study each) |
| Study designs | Human observational comparative studies or clinical trials; English | 32 case-control studies |
| Timing | Not specified | Not specified |