Nerve Growth Factor and Pain Mechanisms

Denk, Franziska; Bennett, David L.H.; McMahon, Stephen B.

doi:10.1146/annurev-neuro-072116-031121

Cited by 203 publications

(212 citation statements)

References 123 publications

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“…Forty years after its discovery, it was recognized that, in addition to its role as a growth factor for cells in the peripheral nervous system, NGF is a key mediator of acute and chronic pain. Different biological actions of NGF contribute to its pro-algesic effects, including NGF-induced sensitization of peripheral nociceptive terminals and NGF-induced sprouting of sensory nerves (for a comprehensive review of NGF biology, please see (9)).…”

mentioning

confidence: 99%

Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?

Miller

Block

Malfait

2017

Current Opinion in Rheumatology

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Purpose of review Anti-NGF antibodies hold tremendous potential for the management of osteoarthritis (OA) pain, but clinical trials have revealed serious adverse effects that are incompletely understood. This review discusses clinical trial results along with preclinical studies that have assessed NGF blockade in experimental OA, in order to provide insight for future studies. Recent findings Systematic reviews have revealed that anti-NGF therapy, including tanezumab, is efficacious in improving pain and function, but serious adverse events, including rapidly progressive OA and osteonecrosis, resulted in a moratorium on trials that was only recently lifted. Within the past year, preclinical testing has revealed effects of NGF blockade on both pain behaviors and joint structure in experimental models of OA. Similar to clinical trial results, these studies in laboratory animals demonstrated analgesic efficacy of NGF blockade. Interestingly, several animal studies have suggested detrimental effects on joint integrity as a result of treatment, particularly when treatment is started early in the disease, when joint damage is mild to moderate. Summary NGF blockade continues to represent a promising new approach for the treatment of OA pain, but the actual benefits and risks remain to be fully elucidated. Preclinical models may suggest patient populations that could be best served while limiting side effects, but future work should further investigate the mechanisms of benefits and unwanted side effects.

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mentioning

confidence: 99%

Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?

Miller

Block

Malfait

2017

Current Opinion in Rheumatology

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“…VEGF has been implicated in angiogenesis associated with arthritis and skeletal metastases [62, 47]. NGF has been implicated in peripheral sensitization through mechanisms such as upregulation of key channels such as sodium channels and transducers that regulate neural activity and by phosphorylation of transducers such as TRPV1 within neurons leading to enhanced activity and increased neuronal excitability [63]. In addition, NGF has been shown to mediate pathological sprouting of nociceptive and sympathetic fibers within the bone and joint across various rodent models of bone and joint pain including cancer-induced bone pain [7], arthritis [64] and fracture [65, 66].…”

Section: Site Of Injury or Pathologymentioning

confidence: 99%

Mechanisms Underlying Bone and Joint Pain

Havelin

King

2018

Curr Osteoporos Rep

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Purpose of Review. The goal of this review is to provide a broad overview of the current understanding of mechanisms underlying bone and joint pain. Recent Findings. Bone or joint pathology is generally accompanied by local release of pro-inflammatory cytokines, growth factors and neurotransmitters that activate and sensitize sensory nerves resulting in an amplified pain signal. Modulation of the pain signal within the spinal cord and brain that result in net increased facilitation is proposed to contribute to the development of chronic pain. Summary. Great strides have been made in our understanding of mechanisms underlying bone and joint pain that will guide development of improved therapeutic options for these patients. Continued research is required for improved understanding of mechanistic differences driving different components of bone and/or joint pain such as movement related pain compared to persistent background pain. Advances will guide development of more individualized and comprehensive therapeutic options.

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“…In this study, we focused on two mechanisms, nerve growth factor (NGF) and opioids. Extensive evidence suggests that NGF is an important pain mediator . NGF was reported to play an important role in visceral hypersensitivity in both patients with irritable bowel syndrome (IBS) and rodent model of IBS .…”

Section: Introductionmentioning

confidence: 99%

“…Extensive evidence suggests that NGF is an important pain mediator. [41][42][43][44] NGF was reported to play an important role in visceral hypersensitivity in both patients with irritable bowel syndrome (IBS) and rodent model of IBS. [45][46][47][48] NGF was also reported to be associated with gastric hypersensitivity in rats treated for colon inflammation.…”

Section: Introductionmentioning

confidence: 99%

Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity

Yan

Yin

et al. 2019

Neurogastroenterology Motil

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Background Gastric electrical stimulation (GES) has been applied to treat gastric motility disorders for decades. This study was designed to investigate the effects and mechanisms of GES for visceral hypersensitivity in a rodent model of functional dyspepsia (FD). Methods Male Sprague‐Dawley rat pups at 10‐days old received 0.1% iodoacetamide (IA) daily for 6 days. The experiments were performed when the rats reached 8‐11 weeks of age, and visceral hypersensitivity was established. Then, GES parameters were optimized and the chronic effects of GES on gastric hypersensitivity were assessed by electromyogram (EMG). Naloxone (3 mg/kg), D‐Phe‐Cys‐Tyr‐D‐Trp‐Orn‐Thr‐Pen‐Thr‐NH2 (CTOP, 1 mg/kg), and anti‐NGF (16 μg/kg) were individually intraperitoneally injected to investigate opioid and nerve growth factor (NGF) mechanisms. Tissues were analyzed for NGF expression. Key Results In the IA‐treated rats, the visceromotor response to gastric distension was significantly increased, and both acute GES with optimized stimulation parameters (0.25 seconds on, 0.25 seconds off, 100 Hz, 0.25 ms, 6 mA) and chronic GES (7 days, 2 hours/day) normalized gastric hypersensitivity. The inhibitory effect of GES on gastric hypersensitivity was blocked by naloxone and CTOP. Anti‐NGF normalized EMG responses in IA‐treated rats. The expressions of NGF in the tissues of IA‐treated rats were dramatically increased, and these increases were suppressed with GES. Conclusions and Inferences GES with optimized parameters improves gastric hypersensitivity induced by neonatal treatment of IA mediated peripherally by suppressing NGF and via the opioid mechanism involving the µ receptor. GES as a potential therapy for treating visceral pain may be explored in clinical studies.

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Nerve Growth Factor and Pain Mechanisms

Cited by 203 publications

References 123 publications

Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?

Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?

Mechanisms Underlying Bone and Joint Pain

Ameliorating effects of optimized gastric electrical stimulation and mechanisms involving nerve growth factor and opioids in a rodent model of gastric hypersensitivity

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