The heat shock cognate 71 kda protein (Hsc70) is a stress-inducible aTPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TrPV1) is a well-documented nociceptor. notably, Hsc70 can inhibit TrPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stress-induced hyperalgesia remains unclear. in the present study, the participation of Hsc70 and its regulator microrna (mir)-3120 were investigated in forced swim (FS) stress-induced mechanical hyperalgesia in rats in an inflammatory state. complete Freund's adjuvant (cFa) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + cFa rats, FS stress was performed for 3 days before cFa injection. The levels of Hsc70, mir-3120 and their downstream molecule TrPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcription-quantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFA-induced mechanical pain. Furthermore, cFa upregulated Hsc70 and TrPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. in FS + cFa rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (lV-Hsc70) could decrease TrPV1 expression and improve the mechanical pain. additionally, the expression level of mir-3120, a regulator of Hsc70, was markedly upregulated on day 3 following FS stress. Finally, miR-3120 was identified to be colocalized with Hsc70 and expressed in all sizes of drG neurons. in cFa rats, drG injection of mir-3120 agomir to induce overexpression of mir-3120 resulted in similar TrPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of lV-Hsc70. These findings suggested that miR-3120/Hsc70 may participate in FS stress-induced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the drG neurons.