Transforming Growth Factor-β in Normal Nociceptive Processing and Pathological Pain Models

Abstract

The transforming growth factor-β (TGF-β) superfamily is a multifunctional, contextually acting family of cytokines that participate in the regulation of development, disease and tissue repair in the nervous system. The TGF-β family is composed of several members, including TGF-βs, bone morphogenetic proteins (BMPs) and activins. In this review, we discuss recent findings that suggest TGF-β function as important pleiotropic modulators of nociceptive processing both physiologically and under pathological painful conditions. The strategy of increasing TGF-β signaling by deleting "BMP and activin membrane-bound inhibitor" (BAMBI), a TGF-β pseudoreceptor, has demonstrated the inhibitory role of TGF-β signaling pathways in normal nociception and in inflammatory and neuropathic pain models. In particular, strong evidence suggests that TGF-β1 is a relevant mediator of nociception and has protective effects against the development of chronic neuropathic pain by inhibiting the neuroimmune responses of neurons and glia and promoting the expression of endogenous opioids within the spinal cord. In the peripheral nervous system, activins and BMPs function as target-derived differentiation factors that determine and maintain the phenotypic identity and circuit assembly of peptidergic nociceptors. In this context, activin is involved in the complex events of neuroinflammation that modulate the expression of pain during wound healing. These findings have provided new insights into the physiopathology of nociception. Moreover, specific members of the TGF-β family and their signaling effectors and modulator molecules may be promising molecular targets for novel therapeutic agents for pain management.

Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

“…An increase in TGF-β 1 during AMI with greater pain intensity can therefore be assumed to have no negative effect on prognosis. TGF-β is known to be a significant mediator of nociception and to have protective effects against the development of chronic neuropathic pain [41] . The effect we found could therefore be part of a physiological counterregulation set off by acute pain.…”

Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis

“…Ligand binding can also be enhanced through a third coreceptor (T␤R-3) that lacks an intracellular signaling domain (52). To propagate an intracellular signal, intrinsic serine/ threonine kinase activity of T␤R-2 transphosphorylates T␤R-1 to initiate receptor-regulated SMAD-dependent or SMADindependent transduction pathways (33).…”

The effect of perioperative analgesic drugs omnopon and dexketoprofen on the functional activity of immune cells in murine model of tumor surgery

“…Differences in TGF-β gene expression changes between control mice and those receiving analgesia in perioperative period may be due to the involvement of this cytokine in pain modulation during trauma and recovery. Thus, systemic administration of a TGF-β neutralizing antibody was shown to enhance mechanical allodynia in mice after sciatic nerve injury [14], as well as modulate pain severity in λ-carrageenan-induced inflammation in rat model [15].…”