Neural Networks 21 (2008) 241–249 www.elsevier.com/locate/neunet 2008 Special Issue Incorporating synaptic time-dependent plasticity and dynamic synapse into a computational model of wind-up ✩ Aydin Farajidavar a , Sohrab Saeb b,∗ , Khosrow Behbehani a a Department of Biomedical Engineering, University of Texas at Arlington, TX 76019, USA b Faculty of Biomedical Engineering, Amirkabir University of Technology, 15875 Tehran, Iran Received 9 August 2007; received in revised form 29 November 2007; accepted 3 December 2007 Abstract “Wind-up”, a condition related to chronic pain, is a form of plasticity in spinal dorsal horn that can be observed during electrical stimulation of pain receptors at low frequencies (0.3–3 Hz). In this paper, we present a computational model to explain several aspects of wind-up. The core of this model is the interplay of spike-time-dependent plasticity (STDP), short-term synaptic plasticity (STP), and different propagation velocities of the three afferent fibers (C, Aδ, and Aβ ). We utilize Izhikevich’s simple spiking neuron to model a dorsal horn neuron (DHN) of the spinal cord. To achieve the expected results, the model parameters need to adapt to the frequency response which is motivated by biological results. The adaptation is performed by a genetic algorithm (GA), and the resulting optimized values interestingly lie in biological ranges. Based on the proposed model, we suggest that STP may be the origin of the band-pass behavior of wind-up between 0.3 and 3 Hz; while the STDP-based long-term plasticity can be responsible for the synaptic potentiation leading to wind-up, or similar phenomena such as central sensitization. Understanding the mechanisms underlying wind-up generation might allow clarification of the molecular mechanisms of pain signaling and development of strategies, such as transcutaneous electrical nerve stimulation (TENS), for pain treatment. c  2007 Elsevier Ltd. All rights reserved. Keywords: Wind-up; Chronic pain; Dynamic synapse; Spik-time-dependent plasticity; Genetic algorithm 1. Introduction The concept of pain plays an important role in everyday life of human beings. Pain is the result of the information transmitted from the pain receptors (nociceptors) to the dorsal horn neurons (DHNs) of the spinal cord, and subsequently to the brain. Nociceptors include different types, among which free nerve endings play an important role in the study of pain (Melzack & Wall, 1965). Stimulation of nociceptors causes pain impulses travel along nerve fibers through several areas of the spinal cord. There are two types of nociceptive afferents, C and Aδ, which carry the impulses of pain. These fibers have small diameters between 0.25–1.5 and 1–5 μm, respectively, and ✩ An abbreviated version of some portions of this article appeared in Saeb, Farajidavar, and Gharibzadeh (2007) as part of the IJCNN 2007 Conference Proceedings, published under IEE copyright. ∗ Corresponding address: No. 31, W. Armaghan St, Valiasr Ave, 19678- 14911 Tehran, Iran. Fax: +98 21 2266 0539. E-mail address: sohrabsaeb@bme.aut.ac.ir (S. Saeb). conduct impulses with different velocities of about 1 and 10 m s −1 , respectively. C and Aδ fibers connect to substantia gelatinosa (SG) and to the deeper cells in the dorsal horn. Pain is not simply a direct result of the activity of nociceptive afferent fibers, but is regulated by other afferent fibers ( Aβ fibers) that are not directly concerned with the transmission of nociceptive information (Willis, Sluka, Rees, & Westlund, 1996). The idea that pain results from the balance of activity in nociceptive and non-nociceptive afferents was formulated in the 1960s and was called the gate control theory (GCT). The theory includes that stimulating Aδ and C fibers causes pain in dorsal horn neurons while stimulating Aβ fibers usually inhibits the pain inputs from the spinal cord dorsal horn neurons. Simply put, non-nociceptive afferents “close” and nociceptive afferents “open” a gate to the central transmission of noxious input (Melzack & Wall, 1965). The gate control theory also provides a neurophysiological basis for the observation that a vibratory stimulus which selectively activates large-diameter afferents can reduce pain. The gate control theory is the rationale for the use of transcutaneous electrical stimulation 0893-6080/$ - see front matter c  2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neunet.2007.12.021