IGF/IGF-1R signal pathway in pain: a promising therapeutic target

Abstract

Pain, one of the most important problems in the field of medicine and public health, has great research significance. Opioids are still the main drugs to relieve pain now. However, its application is limited due to its obvious side effects. Therefore, it is urgent to develop new drugs to relieve pain. Multiple studies have found that IGF/IGF-1R pathway plays an important role in the occurrence and development of pain. The regulation of IGF/IGF-1R pathway has obvious effect on pain. This review summarized and discussed the therapeutic potential of IGF/IGF-1R signal pathway for pain. It also summarized that IGF/IGF-1R regulates pain by acting on neuronal excitability, neuroinflammation, glial cells, apoptosis, etc. However, its mechanisms of occurrence and development in pain still need further study in the future. In conclusion, although more deep researches are needed, these studies indicate that IGF/IGF-1R signal pathway is a promising therapeutic target for pain.

Opposite effects of acute and chronic IGF1 on rat dorsal root ganglion neuron excitability

“…A large panel of studies indicate that IGF1- and IGF-1R are expressed in small-diameter nociceptive DRGs and in spinal dorsal horn neurons ( Craner et al, 2002 ; Hawkes and Kar, 2002 ; Dai et al, 2009 ; Takayama et al, 2011 ; Li et al, 2013 ; Wang et al, 2014 ; Zhang et al, 2014 ; Zhu et al, 2018 ; Tang et al, 2019 ; Ma et al, 2023 ). These neuronal cells convey pain signals from the peripheral to the central DRG terminals and project via the superficial layers of the spinal dorsal horn to higher brain centers of the CNS.…”

“…Altogether, our data suggest that in vitro IGF-1 exerts complex effects on DRG neuron excitability as revealed by its dual and opposite actions upon acute and chronic exposures. This feature probably reflects the complexity of IGF-1 action in vivo , where many studies showed that the peripheral IGF-1/IGF-1R pathway mostly plays a role in promoting pain, while the central (spinal cord) IGF-1/IGF-1R pathway mainly play a role in relieving pain ( Ma et al, 2023 ). Regarding its complexity, the IGF-1/IGF-1R system may not be an optimal target for the clinical treatment of chronic pain.…”

“…In addition to their presence in the CNS, IGF-1 and IGF-IR are also expressed in the peripheral nervous system, notably in the sensory dorsal root ganglion (DRG) nociceptive neurons that convey pain modalities. Many lines of evidence indicate that IGF1- and IGF-1R are expressed in small-diameter nociceptive DRGs and in spinal dorsal horn neurons that are closely related to pain signals ( Craner et al, 2002 ; Hawkes and Kar, 2002 ; Dai et al, 2009 ; Takayama et al, 2011 ; Li et al, 2013 ; Wang et al, 2014 ; Zhang et al, 2014 ; Zhu et al, 2018 ; Tang et al, 2019 ; Ma et al, 2023 ).…”

“…Many studies have found that the IGF-1/IGF-1R pathway can exert opposite actions on pain signals. Several works demonstrate that the IGF-1R signaling aggravates acute and chronic pain while others show that it is involved in relieving chronic pain ( Ma et al, 2023 ). Although it is clear that the IGF-1R signaling tunes pain sensitivity, its modulation of two other important players of pain signals, the TRPV1 and M-type K + channel remains unexplored yet.…”

The multifaceted role of insulin-like growth factor binding protein 7

“…IGFBPs, a family of proteins that bind to insulin-like growth factors (IGFs) and regulate their biological activity, play a crucial role in the IGF signaling pathway ( Ma et al, 2023 ). By binding to IGFs, IGFBPs modulate their biological activity and availability, prolonging their half-life in vivo and regulating their access to IGF receptors, thus impacting the activity of the IGF signaling pathway and regulating biological processes such as cell growth, proliferation, and apoptosis ( Baxter, 2023 ; Galal et al, 2023 ; Werner, 2023 ).…”