Papers of the Week

There is strong evidence that spinoparabrachial neurons in the superficial dorsal horn contribute to persistent pain states, and that the lateral parabrachial complex (PB) conveys relevant nociceptive information to higher structures. The role of PB itself in hyperalgesia and how it recruits descending facilitation has nevertheless received significantly less attention. The current study is a first step towards delineating the functional dynamics of PB and its link to descending control in acute and persistent inflammatory pain. In lightly anesthetized rats, we recorded behavioral withdrawal evoked by mechanical stimulation of the hindpaw, and simultaneously, activity of identified pain-modulating neurons, "ON-cells" and "OFF-cells," in the rostral ventromedial medulla (RVM). This was done before and after inactivation of PB, or to an inflamed paw (1 h, 1 d, or 5-6 d after intraplantar injection of Complete Freund's adjuvant, CFA). Inactivation of but not PB interfered with nociceptive input to RVM under basal conditions, as well as in acute inflammation. By contrast, blocking , but not , PB in established inflammation interfered with behavioral hyperalgesia and ON- and OFF-cell responses. Lesion of PB prior to CFA injection prevented this recruitment of PB in persistent inflammation. These experiments show that PB is required to initiate hyperalgesia, which is then maintained by PB, most likely in both cases via engagement of pain-modulating neurons of the RVM.The lateral parabrachial complex (PB) relays nociceptive information to brain circuits important for transmission and modulation of pain, but its specific role in persistent pain and engagement of descending control mechanisms has received relatively little attention. We show here that PB and to an inflammatory insult demonstrate different functions as inflammation persists, likely by engaging pain-facilitating neurons of the rostral ventromedial medulla. While the PB, the target of the major spinoparabrachial pathway, relays acute nociceptive information, the PB is recruited or unmasked in persistent inflammation to maintain hyperalgesia. These data point to plasticity in the PB itself or its direct and indirect connections with pain-modulating systems as central to development and maintenance of persistent pain.