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. 2010 Dec 8;30(49):16459–16468. doi: 10.1523/JNEUROSCI.3748-10.2010

Figure 4.

Figure 4.

Chronic SNC80 and ARM390 both produce analgesic cross-tolerance. SNC80-tolerant mice were challenged with ARM390 (10 mg/kg), and ARM390-tolerant mice were challenged with SNC80 (10 mg/kg). Graphs show tolerance and cross-tolerance data. A, CFA paw, mechanical response in DOR-eGFP mice. B, CFA tail, thermal response in C57BL/6J wild-type mice. Dashed lines represent baseline mechanical responses pre-CFA. n = 5 mice/group. Cross-tolerance occurs in both treatment groups. C, Repeated nociceptive testing produced associative tolerance. Inflammatory pain was induced in the paw of C57BL/6J mice, and 48 h later they were either tested daily for 5 d with vehicle (tested) or left in their home cage (novice). On day 6, mice were challenged with vehicle, SNC80 (10 mg/kg), or ARM390 (10 mg/kg). Dashed lines represent baseline mechanical responses pre-CFA. n = 5–6 mice/group. Antiallodynic effects of SNC80 or ARM390 were reduced in the habituated (tested) groups compared with corresponding novice drug groups (*p < 0.05, **p < 0.01), indicating that associative tolerance had developed. Nevertheless, in the habituated/tested animals, the two agonists continued to produce significant antiallodynic effects (##p < 0.01 compared with habituated vehicle controls), demonstrating that associative tolerance only partially accounts for the full tolerance and cross-tolerance observed in chronically SNC80- or ARM390-treated animals.