The locus coeruleus (LC), a primary source of noradrenergic (NE) input to the spinal cord, is usually associated with descending pain inhibition, but recent studies have suggested the LC contributes to pain facilitation. To test hypotheses that the LC contributes to allodynia and hyperalgesia in a rodent model of peripheral neuropathic pain, we examined the effect of reversible inactivation of the LC using a local anesthetic (Expt 1) and noradrenergic lesions of the LC using anti-DBH-saporin (Expt 2). In Expt 1, male rats were implanted with bilateral guide cannulae aimed above the LC. Rats were tested for hypersensitivity to mechanical stimuli prior to both SNI and drug administration. 14 d following transection of the tibial and common peroneal nerves leaving the sural branch intact (SNI), 4% lidocaine or saline was bilaterally injected in the LC followed by tests for mechanical allodynia [using von Frey hairs and a machine mounted probe (Ugo Basile)] cold allodynia (plantar application of acetone), and mechanical hyperalgesia (plantar pin prick). Lidocaine reduced allodynia and hyperalgesia at 15 and 45 min (p's < .05); hypersensitivity returned to pre-drug values within 90 min. These results indicate that the LC contributes to the maintenance of neuropathic pain. In Expt 2, anti-dopamine-beta-hydroxylase-saporin or IgG-saporin (control) was administered intracerebroventricularly, prior to nerve injury. After two wk, SNI surgery was performed, and then behavior was re-assessed at 7, 14, 21, and 28 d. Dopamine-beta-hydroxylase immunohistochemistry confirmed LC lesions in all but one animal, which was removed from the analysis. LC lesions did not change responses at the contralateral paw (p's > .05), but reduced allodynia and hyperalgesia at every time point. We conclude that the LC contributes to the development and maintenance of neuropathic pain.