Chronic pain, both inflammatory (pain associated with tissue injury/inflammation) and neuropathic (pain associated with nerve injury/dysfunction), can be devastating and constitute a major health problem. Spontaneous/ongoing pain (stimulus-independent pain) is arguably the most debilitating aspect of neuropathic pain in humans. It is unavoidable and commonly occurs even without hyperalgesia. Despite its clinical importance spontaneous neuropathic pain remains very hard to treat because its underlying mechanisms are surprisingly poorly understood, possibly because most animal studies have focused exclusively on the more easily quantified evoked pain behaviours. Using an animal (rat) model of neuropathic pain that shows significant spontaneous foot lifting (a sign of spontaneous pain in animals), we have recently shown that the amount of spontaneous pain behaviour is related to rate of spontaneous activity in a subpopulation of uninjured C-nociceptors with intact fibres commingling with damaged afferent fibres (Djouhri et al. 2006). This had not been described before probably because most investigations have focused on injured rather than uninjured neurons. The animal model we used was termed modified Spinal Nerve Axotomy (mSNA) which involves in addition to L5 spinal nerve axotomy (SNA) loose ligation of the adjacent L4 spinal nerve with inflammation-inducing chromic gut)(see Djouhri et al., 2006). For electrophysiological experiments we used female rats (150-180g) anaesthetised with pentobarbitone (60 mg kg-1, i.p.), paralysed with pancuronium (0.5 mg/kg i.a.) and artificially ventilated. End-tidal CO2 was maintained at about 4% and blood pressure was usually >80 mmHg (see Djouhri et al., 2006). We also found a similar correlation between the rate of spontaneous activity in C nociceptors and spontaneous pain behaviour in an animal model of chronic inflammatory pain. These findings will be presented together with some preliminary results showing that the hyperpolarisation-activated cyclic nucleotide gated (HCN) channels, which mediate the hypeoplarization activate current (Ih), may contribute to spontaneous activity generation in nociceptive primary afferent neurons and thereby spontaneous pain associated with tissue inflammation and nerve injury.